Logo of moiJournal's HomeManuscript SubmissionAims and ScopeAuthor GuidelinesEditorial BoardHome
Mediators Inflamm. 2001 Apr; 10(2): 51–59.
PMCID: PMC1781697

Anti-inflammatory cytokines in asthma and allergy: interleukin-10, interleukin-12, interferon-gamma.


Interleukin-10 (IL-10) is a cytokine derived from CD4+ T-helper type 2 (T(H2)) cells identified as a suppressor of cytokines from T-helper type 1(T(H1)) cells. Interleukin-12 (IL-12) is produced by B cells, macrophages and dendritic cells, and primarily regulates T(H1) cell differentiation, while suppressing the expansion of T(H2) cell clones. Interferon-gamma (IFN-gamma) is a product of T(H1) cells and exerts inhibitory effects on T(H2) cell differentiation. These cytokines have been implicated in the pathogenesis of asthma and allergies. In this context, IL-12 and IFN-gamma production in asthma have been found to be decreased, and this may reduce their capacity to inhibit IgE synthesis and allergic inflammation. IL-10 is a potent inhibitor of monocyte/macrophage function, suppressing the production of many pro-inflammatory cytokines. A relative underproduction of IL-10 from alveolar macrophages of atopic asthmatics has been reported. Therapeutic modulation of T(H1)/T(H2) imbalance in asthma and allergy by mycobacterial vaccine, specific immunotherapy and cytoline-guanosine dinucleotide motif may lead to increases in IL-12 and IFN-gamma production. Stimulation of IL-10 production by antigen-specific T-cells during immunotherapy may lead to anergy through inhibition of CD28-costimulatory molecule signalling by IL-10s anti-inflammatory effect on basophils, mast cells and eosinophils.

Full Text

The Full Text of this article is available as a PDF (191K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Djukanović R, Roche WR, Wilson JW, Beasley CR, Twentyman OP, Howarth RH, Holgate ST. Mucosal inflammation in asthma. Am Rev Respir Dis. 1990 Aug;142(2):434–457. [PubMed]
  • Azzawi M, Bradley B, Jeffery PK, Frew AJ, Wardlaw AJ, Knowles G, Assoufi B, Collins JV, Durham S, Kay AB. Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma. Am Rev Respir Dis. 1990 Dec;142(6 Pt 1):1407–1413. [PubMed]
  • Bousquet J, Chanez P, Lacoste JY, Barnéon G, Ghavanian N, Enander I, Venge P, Ahlstedt S, Simony-Lafontaine J, Godard P, et al. Eosinophilic inflammation in asthma. N Engl J Med. 1990 Oct 11;323(15):1033–1039. [PubMed]
  • Bousquet J, Jeffery PK, Busse WW, Johnson M, Vignola AM. Asthma. From bronchoconstriction to airways inflammation and remodeling. Am J Respir Crit Care Med. 2000 May;161(5):1720–1745. [PubMed]
  • Redington AE, Howarth PH. Airway wall remodelling in asthma. Thorax. 1997 Apr;52(4):310–312. [PMC free article] [PubMed]
  • Chung KF, Barnes PJ. Cytokines in asthma. Thorax. 1999 Sep;54(9):825–857. [PMC free article] [PubMed]
  • Green JM. The B7/CD28/CTLA4 T-cell activation pathway. Implications for inflammatory lung disease. Am J Respir Cell Mol Biol. 2000 Mar;22(3):261–264. [PubMed]
  • Harding FA, McArthur JG, Gross JA, Raulet DH, Allison JP. CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature. 1992 Apr 16;356(6370):607–609. [PubMed]
  • Walunas TL, Lenschow DJ, Bakker CY, Linsley PS, Freeman GJ, Green JM, Thompson CB, Bluestone JA. CTLA-4 can function as a negative regulator of T cell activation. Immunity. 1994 Aug;1(5):405–413. [PubMed]
  • Oosterwegel MA, Mandelbrot DA, Boyd SD, Lorsbach RB, Jarrett DY, Abbas AK, Sharpe AH. The role of CTLA-4 in regulating Th2 differentiation. J Immunol. 1999 Sep 1;163(5):2634–2639. [PubMed]
  • Huang TJ, MacAry PA, Eynott P, Moussavi A, Daniel KC, Askenase PW, Kemeny DM, Chung KF. Allergen-specific Th1 cells counteract efferent Th2 cell-dependent bronchial hyperresponsiveness and eosinophilic inflammation partly via IFN-gamma. J Immunol. 2001 Jan 1;166(1):207–217. [PubMed]
  • Cohn L, Homer RJ, Niu N, Bottomly K. T helper 1 cells and interferon gamma regulate allergic airway inflammation and mucus production. J Exp Med. 1999 Nov 1;190(9):1309–1318. [PMC free article] [PubMed]
  • Prescott SL, Macaubas C, Smallacombe T, Holt BJ, Sly PD, Holt PG. Development of allergen-specific T-cell memory in atopic and normal children. Lancet. 1999 Jan 16;353(9148):196–200. [PubMed]
  • Prescott SL, Macaubas C, Holt BJ, Smallacombe TB, Loh R, Sly PD, Holt PG. Transplacental priming of the human immune system to environmental allergens: universal skewing of initial T cell responses toward the Th2 cytokine profile. J Immunol. 1998 May 15;160(10):4730–4737. [PubMed]
  • Shirakawa T, Enomoto T, Shimazu S, Hopkin JM. The inverse association between tuberculin responses and atopic disorder. Science. 1997 Jan 3;275(5296):77–79. [PubMed]
  • Matricardi PM, Rosmini F, Rapicetta M, Gasbarrini G, Stroffolini T. Atopy, hygiene, and anthroposophic lifestyle. San Marino Study Group. Lancet. 1999 Jul 31;354(9176):430–430. [PubMed]
  • Gerrard JW, Geddes CA, Reggin PL, Gerrard CD, Horne S. Serum IgE levels in white and metis communities in Saskatchewan. Ann Allergy. 1976 Aug;37(2):91–100. [PubMed]
  • Gustafsson D, Andersson K, Fagerlund I, Kjellman NI. Significance of indoor environment for the development of allergic symptoms in children followed up to 18 months of age. Allergy. 1996 Nov;51(11):789–795. [PubMed]
  • van Halteren AG, van der Cammen MJ, Cooper D, Savelkoul HF, Kraal G, Holt PG. Regulation of antigen-specific IgE, IgG1, and mast cell responses to ingested allergen by mucosal tolerance induction. J Immunol. 1997 Sep 15;159(6):3009–3015. [PubMed]
  • Holt PG. Primary allergic sensitization to environmental antigens: perinatal T cell priming as a determinant of responder phenotype in adulthood. J Exp Med. 1996 Apr 1;183(4):1297–1301. [PMC free article] [PubMed]
  • Müller U, Akdis CA, Fricker M, Akdis M, Blesken T, Bettens F, Blaser K. Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase A2 induces specific T-cell anergy in patients allergic to bee venom. J Allergy Clin Immunol. 1998 Jun;101(6 Pt 1):747–754. [PubMed]
  • Bousquet J, Lockey R, Malling HJ. Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. J Allergy Clin Immunol. 1998 Oct;102(4 Pt 1):558–562. [PubMed]
  • Abramson M, Puy R, Weiner J. Immunotherapy in asthma: an updated systematic review. Allergy. 1999 Oct;54(10):1022–1041. [PubMed]
  • Durham SR, Walker SM, Varga EM, Jacobson MR, O'Brien F, Noble W, Till SJ, Hamid QA, Nouri-Aria KT. Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med. 1999 Aug 12;341(7):468–475. [PubMed]
  • Jutel M, Pichler WJ, Skrbic D, Urwyler A, Dahinden C, Müller UR. Bee venom immunotherapy results in decrease of IL-4 and IL-5 and increase of IFN-gamma secretion in specific allergen-stimulated T cell cultures. J Immunol. 1995 Apr 15;154(8):4187–4194. [PubMed]
  • Secrist H, Chelen CJ, Wen Y, Marshall JD, Umetsu DT. Allergen immunotherapy decreases interleukin 4 production in CD4+ T cells from allergic individuals. J Exp Med. 1993 Dec 1;178(6):2123–2130. [PMC free article] [PubMed]
  • Bellinghausen I, Metz G, Enk AH, Christmann S, Knop J, Saloga J. Insect venom immunotherapy induces interleukin-10 production and a Th2-to-Th1 shift, and changes surface marker expression in venom-allergic subjects. Eur J Immunol. 1997 May;27(5):1131–1139. [PubMed]
  • Akdis CA, Blaser K. Mechanisms of allergen-specific immunotherapy. Allergy. 2000 Jun;55(6):522–530. [PubMed]
  • Akdis CA, Blesken T, Akdis M, Wüthrich B, Blaser K. Role of interleukin 10 in specific immunotherapy. J Clin Invest. 1998 Jul 1;102(1):98–106. [PMC free article] [PubMed]
  • Becker JC, Czerny C, Bröcker EB. Maintenance of clonal anergy by endogenously produced IL-10. Int Immunol. 1994 Oct;6(10):1605–1612. [PubMed]
  • Enk AH, Saloga J, Becker D, Mohamadzadeh M, Knop J. Induction of hapten-specific tolerance by interleukin 10 in vivo. J Exp Med. 1994 Apr 1;179(4):1397–1402. [PMC free article] [PubMed]
  • Del Prete G, De Carli M, Almerigogna F, Giudizi MG, Biagiotti R, Romagnani S. Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. J Immunol. 1993 Jan 15;150(2):353–360. [PubMed]
  • Punnonen J, de Waal Malefyt R, van Vlasselaer P, Gauchat JF, de Vries JE. IL-10 and viral IL-10 prevent IL-4-induced IgE synthesis by inhibiting the accessory cell function of monocytes. J Immunol. 1993 Aug 1;151(3):1280–1289. [PubMed]
  • Hamid QA, Schotman E, Jacobson MR, Walker SM, Durham SR. Increases in IL-12 messenger RNA+ cells accompany inhibition of allergen-induced late skin responses after successful grass pollen immunotherapy. J Allergy Clin Immunol. 1997 Feb;99(2):254–260. [PubMed]
  • Durham SR, Ying S, Varney VA, Jacobson MR, Sudderick RM, Mackay IS, Kay AB, Hamid QA. Grass pollen immunotherapy inhibits allergen-induced infiltration of CD4+ T lymphocytes and eosinophils in the nasal mucosa and increases the number of cells expressing messenger RNA for interferon-gamma. J Allergy Clin Immunol. 1996 Jun;97(6):1356–1365. [PubMed]
  • Erb KJ, Holloway JW, Sobeck A, Moll H, Le Gros G. Infection of mice with Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) suppresses allergen-induced airway eosinophilia. J Exp Med. 1998 Feb 16;187(4):561–569. [PMC free article] [PubMed]
  • Herz U, Gerhold K, Grüber C, Braun A, Wahn U, Renz H, Paul K. BCG infection suppresses allergic sensitization and development of increased airway reactivity in an animal model. J Allergy Clin Immunol. 1998 Nov;102(5):867–874. [PubMed]
  • Wang CC, Rook GA. Inhibition of an established allergic response to ovalbumin in BALB/c mice by killed Mycobacterium vaccae. Immunology. 1998 Mar;93(3):307–313. [PMC free article] [PubMed]
  • Krieg AM. An innate immune defense mechanism based on the recognition of CpG motifs in microbial DNA. J Lab Clin Med. 1996 Aug;128(2):128–133. [PubMed]
  • Kline JN, Waldschmidt TJ, Businga TR, Lemish JE, Weinstock JV, Thorne PS, Krieg AM. Modulation of airway inflammation by CpG oligodeoxynucleotides in a murine model of asthma. J Immunol. 1998 Mar 15;160(6):2555–2559. [PubMed]
  • Broide D, Raz E. DNA-Based immunization for asthma. Int Arch Allergy Immunol. 1999 Feb-Apr;118(2-4):453–456. [PubMed]
  • Broide D, Schwarze J, Tighe H, Gifford T, Nguyen MD, Malek S, Van Uden J, Martin-Orozco E, Gelfand EW, Raz E. Immunostimulatory DNA sequences inhibit IL-5, eosinophilic inflammation, and airway hyperresponsiveness in mice. J Immunol. 1998 Dec 15;161(12):7054–7062. [PubMed]
  • Kline JN, Krieg AM, Waldschmidt TJ, Ballas ZK, Jain V, Businga TR. CpG oligodeoxynucleotides do not require TH1 cytokines to prevent eosinophilic airway inflammation in a murine model of asthma. J Allergy Clin Immunol. 1999 Dec;104(6):1258–1264. [PubMed]
  • Fiorentino DF, Bond MW, Mosmann TR. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989 Dec 1;170(6):2081–2095. [PMC free article] [PubMed]
  • Enk AH, Katz SI. Identification and induction of keratinocyte-derived IL-10. J Immunol. 1992 Jul 1;149(1):92–95. [PubMed]
  • Spits H, de Waal Malefyt R. Functional characterization of human IL-10. Int Arch Allergy Immunol. 1992;99(1):8–15. [PubMed]
  • Berkman N, John M, Roesems G, Jose PJ, Barnes PJ, Chung KF. Inhibition of macrophage inflammatory protein-1 alpha expression by IL-10. Differential sensitivities in human blood monocytes and alveolar macrophages. J Immunol. 1995 Nov 1;155(9):4412–4418. [PubMed]
  • Liu Y, Wei SH, Ho AS, de Waal Malefyt R, Moore KW. Expression cloning and characterization of a human IL-10 receptor. J Immunol. 1994 Feb 15;152(4):1821–1829. [PubMed]
  • Tan JC, Indelicato SR, Narula SK, Zavodny PJ, Chou CC. Characterization of interleukin-10 receptors on human and mouse cells. J Biol Chem. 1993 Oct 5;268(28):21053–21059. [PubMed]
  • Carson WE, Lindemann MJ, Baiocchi R, Linett M, Tan JC, Chou CC, Narula S, Caligiuri MA. The functional characterization of interleukin-10 receptor expression on human natural killer cells. Blood. 1995 Jun 15;85(12):3577–3585. [PubMed]
  • Bazan JF. Structural design and molecular evolution of a cytokine receptor superfamily. Proc Natl Acad Sci U S A. 1990 Sep;87(18):6934–6938. [PMC free article] [PubMed]
  • Ho AS, Liu Y, Khan TA, Hsu DH, Bazan JF, Moore KW. A receptor for interleukin 10 is related to interferon receptors. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11267–11271. [PMC free article] [PubMed]
  • Spencer SD, Di Marco F, Hooley J, Pitts-Meek S, Bauer M, Ryan AM, Sordat B, Gibbs VC, Aguet M. The orphan receptor CRF2-4 is an essential subunit of the interleukin 10 receptor. J Exp Med. 1998 Feb 16;187(4):571–578. [PMC free article] [PubMed]
  • Finbloom DS, Winestock KD. IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes. J Immunol. 1995 Aug 1;155(3):1079–1090. [PubMed]
  • Wehinger J, Gouilleux F, Groner B, Finke J, Mertelsmann R, Weber-Nordt RM. IL-10 induces DNA binding activity of three STAT proteins (Stat1, Stat3, and Stat5) and their distinct combinatorial assembly in the promoters of selected genes. FEBS Lett. 1996 Oct 7;394(3):365–370. [PubMed]
  • Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O'Garra A. IL-10 inhibits cytokine production by activated macrophages. J Immunol. 1991 Dec 1;147(11):3815–3822. [PubMed]
  • de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991 Nov 1;174(5):1209–1220. [PMC free article] [PubMed]
  • Seitz M, Loetscher P, Dewald B, Towbin H, Gallati H, Baggiolini M. Interleukin-10 differentially regulates cytokine inhibitor and chemokine release from blood mononuclear cells and fibroblasts. Eur J Immunol. 1995 Apr;25(4):1129–1132. [PubMed]
  • de Waal Malefyt R, Haanen J, Spits H, Roncarolo MG, te Velde A, Figdor C, Johnson K, Kastelein R, Yssel H, de Vries JE. Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med. 1991 Oct 1;174(4):915–924. [PMC free article] [PubMed]
  • de Waal Malefyt R, Yssel H, Roncarolo MG, Spits H, de Vries JE. Interleukin-10. Curr Opin Immunol. 1992 Jun;4(3):314–320. [PubMed]
  • Cunha FQ, Moncada S, Liew FY. Interleukin-10 (IL-10) inhibits the induction of nitric oxide synthase by interferon-gamma in murine macrophages. Biochem Biophys Res Commun. 1992 Feb 14;182(3):1155–1159. [PubMed]
  • John M, Hirst SJ, Jose PJ, Robichaud A, Berkman N, Witt C, Twort CH, Barnes PJ, Chung KF. Human airway smooth muscle cells express and release RANTES in response to T helper 1 cytokines: regulation by T helper 2 cytokines and corticosteroids. J Immunol. 1997 Feb 15;158(4):1841–1847. [PubMed]
  • John M, Au BT, Jose PJ, Lim S, Saunders M, Barnes PJ, Mitchell JA, Belvisi MG, Chung KF. Expression and release of interleukin-8 by human airway smooth muscle cells: inhibition by Th-2 cytokines and corticosteroids. Am J Respir Cell Mol Biol. 1998 Jan;18(1):84–90. [PubMed]
  • Moore KW, O'Garra A, de Waal Malefyt R, Vieira P, Mosmann TR. Interleukin-10. Annu Rev Immunol. 1993;11:165–190. [PubMed]
  • Schandené L, Alonso-Vega C, Willems F, Gérard C, Delvaux A, Velu T, Devos R, de Boer M, Goldman M. B7/CD28-dependent IL-5 production by human resting T cells is inhibited by IL-10. J Immunol. 1994 May 1;152(9):4368–4374. [PubMed]
  • Akdis CA, Joss A, Akdis M, Faith A, Blaser K. A molecular basis for T cell suppression by IL-10: CD28-associated IL-10 receptor inhibits CD28 tyrosine phosphorylation and phosphatidylinositol 3-kinase binding. FASEB J. 2000 Sep;14(12):1666–1668. [PubMed]
  • Jeannin P, Lecoanet S, Delneste Y, Gauchat JF, Bonnefoy JY. IgE versus IgG4 production can be differentially regulated by IL-10. J Immunol. 1998 Apr 1;160(7):3555–3561. [PubMed]
  • Thompson-Snipes L, Dhar V, Bond MW, Mosmann TR, Moore KW, Rennick DM. Interleukin 10: a novel stimulatory factor for mast cells and their progenitors. J Exp Med. 1991 Feb 1;173(2):507–510. [PMC free article] [PubMed]
  • Chen WF, Zlotnik A. IL-10: a novel cytotoxic T cell differentiation factor. J Immunol. 1991 Jul 15;147(2):528–534. [PubMed]
  • Weber-Nordt RM, Henschler R, Schott E, Wehinger J, Behringer D, Mertelsmann R, Finke J. Interleukin-10 increases Bcl-2 expression and survival in primary human CD34+ hematopoietic progenitor cells. Blood. 1996 Oct 1;88(7):2549–2558. [PubMed]
  • Lacraz S, Nicod LP, Chicheportiche R, Welgus HG, Dayer JM. IL-10 inhibits metalloproteinase and stimulates TIMP-1 production in human mononuclear phagocytes. J Clin Invest. 1995 Nov;96(5):2304–2310. [PMC free article] [PubMed]
  • Borish L, Aarons A, Rumbyrt J, Cvietusa P, Negri J, Wenzel S. Interleukin-10 regulation in normal subjects and patients with asthma. J Allergy Clin Immunol. 1996 Jun;97(6):1288–1296. [PubMed]
  • John M, Lim S, Seybold J, Jose P, Robichaud A, O'Connor B, Barnes PJ, Chung KF. Inhaled corticosteroids increase interleukin-10 but reduce macrophage inflammatory protein-1alpha, granulocyte-macrophage colony-stimulating factor, and interferon-gamma release from alveolar macrophages in asthma. Am J Respir Crit Care Med. 1998 Jan;157(1):256–262. [PubMed]
  • Dugas N, Vouldoukis I, Bécherel P, Arock M, Debré P, Tardieu M, Mossalayi DM, Delfraissy JF, Kolb JP, Dugas B. Triggering of CD23b antigen by anti-CD23 monoclonal antibodies induces interleukin-10 production by human macrophages. Eur J Immunol. 1996 Jun;26(6):1394–1398. [PubMed]
  • Hobbs K, Negri J, Klinnert M, Rosenwasser LJ, Borish L. Interleukin-10 and transforming growth factor-beta promoter polymorphisms in allergies and asthma. Am J Respir Crit Care Med. 1998 Dec;158(6):1958–1962. [PubMed]
  • Mascali JJ, Cvietusa P, Negri J, Borish L. Anti-inflammatory effects of theophylline: modulation of cytokine production. Ann Allergy Asthma Immunol. 1996 Jul;77(1):34–38. [PubMed]
  • Robinson DS, Tsicopoulos A, Meng Q, Durham S, Kay AB, Hamid Q. Increased interleukin-10 messenger RNA expression in atopic allergy and asthma. Am J Respir Cell Mol Biol. 1996 Feb;14(2):113–117. [PubMed]
  • Zuany-Amorim C, Créminon C, Nevers MC, Nahori MA, Vargaftig BB, Pretolani M. Modulation by IL-10 of antigen-induced IL-5 generation, and CD4+ T lymphocyte and eosinophil infiltration into the mouse peritoneal cavity. J Immunol. 1996 Jul 1;157(1):377–384. [PubMed]
  • Zuany-Amorim C, Hailé S, Leduc D, Dumarey C, Huerre M, Vargaftig BB, Pretolani M. Interleukin-10 inhibits antigen-induced cellular recruitment into the airways of sensitized mice. J Clin Invest. 1995 Jun;95(6):2644–2651. [PMC free article] [PubMed]
  • van Scott MR, Justice JP, Bradfield JF, Enright E, Sigounas A, Sur S. IL-10 reduces Th2 cytokine production and eosinophilia but augments airway reactivity in allergic mice. Am J Physiol Lung Cell Mol Physiol. 2000 Apr;278(4):L667–L674. [PubMed]
  • Yang X, Wang S, Fan Y, Han X. IL-10 deficiency prevents IL-5 overproduction and eosinophilic inflammation in a murine model of asthma-like reaction. Eur J Immunol. 2000 Feb;30(2):382–391. [PubMed]
  • Tournoy KG, Kips JC, Pauwels RA. Endogenous interleukin-10 suppresses allergen-induced airway inflammation and nonspecific airway responsiveness. Clin Exp Allergy. 2000 Jun;30(6):775–783. [PubMed]
  • Mäkelä MJ, Kanehiro A, Borish L, Dakhama A, Loader J, Joetham A, Xing Z, Jordana M, Larsen GL, Gelfand EW. IL-10 is necessary for the expression of airway hyperresponsiveness but not pulmonary inflammation after allergic sensitization. Proc Natl Acad Sci U S A. 2000 May 23;97(11):6007–6012. [PMC free article] [PubMed]
  • Groux H, Bigler M, de Vries JE, Roncarolo MG. Interleukin-10 induces a long-term antigen-specific anergic state in human CD4+ T cells. J Exp Med. 1996 Jul 1;184(1):19–29. [PMC free article] [PubMed]
  • Chernoff AE, Granowitz EV, Shapiro L, Vannier E, Lonnemann G, Angel JB, Kennedy JS, Rabson AR, Wolff SM, Dinarello CA. A randomized, controlled trial of IL-10 in humans. Inhibition of inflammatory cytokine production and immune responses. J Immunol. 1995 May 15;154(10):5492–5499. [PubMed]
  • Hemmi S, Böhni R, Stark G, Di Marco F, Aguet M. A novel member of the interferon receptor family complements functionality of the murine interferon gamma receptor in human cells. Cell. 1994 Mar 11;76(5):803–810. [PubMed]
  • Marsters SA, Pennica D, Bach E, Schreiber RD, Ashkenazi A. Interferon gamma signals via a high-affinity multisubunit receptor complex that contains two types of polypeptide chain. Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5401–5405. [PMC free article] [PubMed]
  • Igarashi K, Garotta G, Ozmen L, Ziemiecki A, Wilks AF, Harpur AG, Larner AC, Finbloom DS. Interferon-gamma induces tyrosine phosphorylation of interferon-gamma receptor and regulated association of protein tyrosine kinases, Jak1 and Jak2, with its receptor. J Biol Chem. 1994 May 20;269(20):14333–14336. [PubMed]
  • Sakatsume M, Igarashi K, Winestock KD, Garotta G, Larner AC, Finbloom DS. The Jak kinases differentially associate with the alpha and beta (accessory factor) chains of the interferon gamma receptor to form a functional receptor unit capable of activating STAT transcription factors. J Biol Chem. 1995 Jul 21;270(29):17528–17534. [PubMed]
  • Heim MH, Kerr IM, Stark GR, Darnell JE., Jr Contribution of STAT SH2 groups to specific interferon signaling by the Jak-STAT pathway. Science. 1995 Mar 3;267(5202):1347–1349. [PubMed]
  • Decker T, Lew DJ, Mirkovitch J, Darnell JE., Jr Cytoplasmic activation of GAF, an IFN-gamma-regulated DNA-binding factor. EMBO J. 1991 Apr;10(4):927–932. [PMC free article] [PubMed]
  • Sakamoto H, Yasukawa H, Masuhara M, Tanimura S, Sasaki A, Yuge K, Ohtsubo M, Ohtsuka A, Fujita T, Ohta T, et al. A Janus kinase inhibitor, JAB, is an interferon-gamma-inducible gene and confers resistance to interferons. Blood. 1998 Sep 1;92(5):1668–1676. [PubMed]
  • Romagnani S. Regulation and deregulation of human IgE synthesis. Immunol Today. 1990 Sep;11(9):316–321. [PubMed]
  • Nakajima H, Iwamoto I, Yoshida S. Aerosolized recombinant interferon-gamma prevents antigen-induced eosinophil recruitment in mouse trachea. Am Rev Respir Dis. 1993 Oct;148(4 Pt 1):1102–1104. [PubMed]
  • Gosset P, Tsicopoulos A, Wallaert B, Joseph M, Capron A, Tonnel AB. Tumor necrosis factor alpha and interleukin-6 production by human mononuclear phagocytes from allergic asthmatics after IgE-dependent stimulation. Am Rev Respir Dis. 1992 Sep;146(3):768–774. [PubMed]
  • Gifford GE, Lohmann-Matthes ML. Gamma interferon priming of mouse and human macrophages for induction of tumor necrosis factor production by bacterial lipopolysaccharide. J Natl Cancer Inst. 1987 Jan;78(1):121–124. [PubMed]
  • Billiau A, Dijkmans R. Interferon-gamma: mechanism of action and therapeutic potential. Biochem Pharmacol. 1990 Oct 1;40(7):1433–1439. [PubMed]
  • Sen GC, Lengyel P. The interferon system. A bird's eye view of its biochemistry. J Biol Chem. 1992 Mar 15;267(8):5017–5020. [PubMed]
  • Gusella GL, Musso T, Bosco MC, Espinoza-Delgado I, Matsushima K, Varesio L. IL-2 up-regulates but IFN-gamma suppresses IL-8 expression in human monocytes. J Immunol. 1993 Sep 1;151(5):2725–2732. [PubMed]
  • Chomarat P, Rissoan MC, Banchereau J, Miossec P. Interferon gamma inhibits interleukin 10 production by monocytes. J Exp Med. 1993 Feb 1;177(2):523–527. [PMC free article] [PubMed]
  • Donnelly RP, Freeman SL, Hayes MP. Inhibition of IL-10 expression by IFN-gamma up-regulates transcription of TNF-alpha in human monocytes. J Immunol. 1995 Aug 1;155(3):1420–1427. [PubMed]
  • Leonard C, Tormey V, Burke C, Poulter LW. Allergen-induced cytokine production in atopic disease and its relationship to disease severity. Am J Respir Cell Mol Biol. 1997 Sep;17(3):368–375. [PubMed]
  • Koning H, Neijens HJ, Baert MR, Oranje AP, Savelkoul HF. T cell subsets and cytokines in allergic and non-allergic children. I. Analysis of IL-4, IFN-gamma and IL-13 mRNA expression and protein production. Cytokine. 1997 Jun;9(6):416–426. [PubMed]
  • Hayden C, Pereira E, Rye P, Palmer L, Gibson N, Palenque M, Hagel I, Lynch N, Goldblatt J, Lesouëf P. Mutation screening of interferon-gamma (IFNgamma) as a candidate gene for asthma. Clin Exp Allergy. 1997 Dec;27(12):1412–1416. [PubMed]
  • Lack G, Bradley KL, Hamelmann E, Renz H, Loader J, Leung DY, Larsen G, Gelfand EW. Nebulized IFN-gamma inhibits the development of secondary allergic responses in mice. J Immunol. 1996 Aug 15;157(4):1432–1439. [PubMed]
  • Iwamoto I, Nakajima H, Endo H, Yoshida S. Interferon gamma regulates antigen-induced eosinophil recruitment into the mouse airways by inhibiting the infiltration of CD4+ T cells. J Exp Med. 1993 Feb 1;177(2):573–576. [PMC free article] [PubMed]
  • Li XM, Chopra RK, Chou TY, Schofield BH, Wills-Karp M, Huang SK. Mucosal IFN-gamma gene transfer inhibits pulmonary allergic responses in mice. J Immunol. 1996 Oct 15;157(8):3216–3219. [PubMed]
  • Coyle AJ, Tsuyuki S, Bertrand C, Huang S, Aguet M, Alkan SS, Anderson GP. Mice lacking the IFN-gamma receptor have impaired ability to resolve a lung eosinophilic inflammatory response associated with a prolonged capacity of T cells to exhibit a Th2 cytokine profile. J Immunol. 1996 Apr 15;156(8):2680–2685. [PubMed]
  • Zuany-Amorim C, Leduc D, Vargaftig BB, Pretolani M. Modulation by rm interferon-gamma and CD4+ T-lymphocytes of allergic eosinophil accumulation in the mice peritoneal cavity. Ann N Y Acad Sci. 1994 May 28;725:34–43. [PubMed]
  • Lack G, Nelson HS, Amran D, Oshiba A, Jung T, Bradley KL, Giclas PC, Gelfand EW. Rush immunotherapy results in allergen-specific alterations in lymphocyte function and interferon-gamma production in CD4+ T cells. J Allergy Clin Immunol. 1997 Apr;99(4):530–538. [PubMed]
  • Durham SR, Till SJ. Immunologic changes associated with allergen immunotherapy. J Allergy Clin Immunol. 1998 Aug;102(2):157–164. [PubMed]
  • Bentley AM, Hamid Q, Robinson DS, Schotman E, Meng Q, Assoufi B, Kay AB, Durham SR. Prednisolone treatment in asthma. Reduction in the numbers of eosinophils, T cells, tryptase-only positive mast cells, and modulation of IL-4, IL-5, and interferon-gamma cytokine gene expression within the bronchial mucosa. Am J Respir Crit Care Med. 1996 Feb;153(2):551–556. [PubMed]
  • Leung DY, Martin RJ, Szefler SJ, Sher ER, Ying S, Kay AB, Hamid Q. Dysregulation of interleukin 4, interleukin 5, and interferon gamma gene expression in steroid-resistant asthma. J Exp Med. 1995 Jan 1;181(1):33–40. [PMC free article] [PubMed]
  • Boguniewicz M, Martin RJ, Martin D, Gibson U, Celniker A, Williams M, Leung DY. The effects of nebulized recombinant interferon-gamma in asthmatic airways. J Allergy Clin Immunol. 1995 Jan;95(1 Pt 1):133–135. [PubMed]
  • Trinchieri G. Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu Rev Immunol. 1995;13:251–276. [PubMed]
  • Macatonia SE, Hosken NA, Litton M, Vieira P, Hsieh CS, Culpepper JA, Wysocka M, Trinchieri G, Murphy KM, O'Garra A. Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells. J Immunol. 1995 May 15;154(10):5071–5079. [PubMed]
  • Nutku E, Gounni AS, Olivenstein R, Hamid Q. Evidence for expression of eosinophil-associated IL-12 messenger RNA and immunoreactivity in bronchial asthma. J Allergy Clin Immunol. 2000 Aug;106(2):288–292. [PubMed]
  • Chua AO, Chizzonite R, Desai BB, Truitt TP, Nunes P, Minetti LJ, Warrier RR, Presky DH, Levine JF, Gately MK, et al. Expression cloning of a human IL-12 receptor component. A new member of the cytokine receptor superfamily with strong homology to gp130. J Immunol. 1994 Jul 1;153(1):128–136. [PubMed]
  • Presky DH, Yang H, Minetti LJ, Chua AO, Nabavi N, Wu CY, Gately MK, Gubler U. A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits. Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14002–14007. [PMC free article] [PubMed]
  • Szabo SJ, Dighe AS, Gubler U, Murphy KM. Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells. J Exp Med. 1997 Mar 3;185(5):817–824. [PMC free article] [PubMed]
  • Rogge L, Barberis-Maino L, Biffi M, Passini N, Presky DH, Gubler U, Sinigaglia F. Selective expression of an interleukin-12 receptor component by human T helper 1 cells. J Exp Med. 1997 Mar 3;185(5):825–831. [PMC free article] [PubMed]
  • Bacon CM, McVicar DW, Ortaldo JR, Rees RC, O'Shea JJ, Johnston JA. Interleukin 12 (IL-12) induces tyrosine phosphorylation of JAK2 and TYK2: differential use of Janus family tyrosine kinases by IL-2 and IL-12. J Exp Med. 1995 Jan 1;181(1):399–404. [PMC free article] [PubMed]
  • Zou J, Presky DH, Wu CY, Gubler U. Differential associations between the cytoplasmic regions of the interleukin-12 receptor subunits beta1 and beta2 and JAK kinases. J Biol Chem. 1997 Feb 28;272(9):6073–6077. [PubMed]
  • Jacobson NG, Szabo SJ, Weber-Nordt RM, Zhong Z, Schreiber RD, Darnell JE, Jr, Murphy KM. Interleukin 12 signaling in T helper type 1 (Th1) cells involves tyrosine phosphorylation of signal transducer and activator of transcription (Stat)3 and Stat4. J Exp Med. 1995 May 1;181(5):1755–1762. [PMC free article] [PubMed]
  • Yu CR, Lin JX, Fink DW, Akira S, Bloom ET, Yamauchi A. Differential utilization of Janus kinase-signal transducer activator of transcription signaling pathways in the stimulation of human natural killer cells by IL-2, IL-12, and IFN-alpha. J Immunol. 1996 Jul 1;157(1):126–137. [PubMed]
  • Robertson MJ, Soiffer RJ, Wolf SF, Manley TJ, Donahue C, Young D, Herrmann SH, Ritz J. Response of human natural killer (NK) cells to NK cell stimulatory factor (NKSF): cytolytic activity and proliferation of NK cells are differentially regulated by NKSF. J Exp Med. 1992 Mar 1;175(3):779–788. [PMC free article] [PubMed]
  • Gately MK, Desai BB, Wolitzky AG, Quinn PM, Dwyer CM, Podlaski FJ, Familletti PC, Sinigaglia F, Chizonnite R, Gubler U, et al. Regulation of human lymphocyte proliferation by a heterodimeric cytokine, IL-12 (cytotoxic lymphocyte maturation factor). J Immunol. 1991 Aug 1;147(3):874–882. [PubMed]
  • Perussia B, Chan SH, D'Andrea A, Tsuji K, Santoli D, Pospisil M, Young D, Wolf SF, Trinchieri G. Natural killer (NK) cell stimulatory factor or IL-12 has differential effects on the proliferation of TCR-alpha beta+, TCR-gamma delta+ T lymphocytes, and NK cells. J Immunol. 1992 Dec 1;149(11):3495–3502. [PubMed]
  • Bertagnolli MM, Lin BY, Young D, Herrmann SH. IL-12 augments antigen-dependent proliferation of activated T lymphocytes. J Immunol. 1992 Dec 15;149(12):3778–3783. [PubMed]
  • Kobayashi M, Fitz L, Ryan M, Hewick RM, Clark SC, Chan S, Loudon R, Sherman F, Perussia B, Trinchieri G. Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J Exp Med. 1989 Sep 1;170(3):827–845. [PMC free article] [PubMed]
  • Gately MK, Wolitzky AG, Quinn PM, Chizzonite R. Regulation of human cytolytic lymphocyte responses by interleukin-12. Cell Immunol. 1992 Aug;143(1):127–142. [PubMed]
  • Wolf SF, Temple PA, Kobayashi M, Young D, Dicig M, Lowe L, Dzialo R, Fitz L, Ferenz C, Hewick RM, et al. Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells. J Immunol. 1991 May 1;146(9):3074–3081. [PubMed]
  • Schoenhaut DS, Chua AO, Wolitzky AG, Quinn PM, Dwyer CM, McComas W, Familletti PC, Gately MK, Gubler U. Cloning and expression of murine IL-12. J Immunol. 1992 Jun 1;148(11):3433–3440. [PubMed]
  • Manetti R, Parronchi P, Giudizi MG, Piccinni MP, Maggi E, Trinchieri G, Romagnani S. Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells. J Exp Med. 1993 Apr 1;177(4):1199–1204. [PMC free article] [PubMed]
  • Hsieh CS, Macatonia SE, Tripp CS, Wolf SF, O'Garra A, Murphy KM. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science. 1993 Apr 23;260(5107):547–549. [PubMed]
  • Kiniwa M, Gately M, Gubler U, Chizzonite R, Fargeas C, Delespesse G. Recombinant interleukin-12 suppresses the synthesis of immunoglobulin E by interleukin-4 stimulated human lymphocytes. J Clin Invest. 1992 Jul;90(1):262–266. [PMC free article] [PubMed]
  • Manetti R, Gerosa F, Giudizi MG, Biagiotti R, Parronchi P, Piccinni MP, Sampognaro S, Maggi E, Romagnani S, Trinchieri G, et al. Interleukin 12 induces stable priming for interferon gamma (IFN-gamma) production during differentiation of human T helper (Th) cells and transient IFN-gamma production in established Th2 cell clones. J Exp Med. 1994 Apr 1;179(4):1273–1283. [PMC free article] [PubMed]
  • Yoshimoto T, Okamura H, Tagawa YI, Iwakura Y, Nakanishi K. Interleukin 18 together with interleukin 12 inhibits IgE production by induction of interferon-gamma production from activated B cells. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3948–3953. [PMC free article] [PubMed]
  • Zhao LL, Lindén A, Sjöstrand M, Cui ZH, Lötvall J, Jordana M. IL-12 regulates bone marrow eosinophilia and airway eotaxin levels induced by airway allergen exposure. Allergy. 2000 Aug;55(8):749–756. [PubMed]
  • Naseer T, Minshall EM, Leung DY, Laberge S, Ernst P, Martin RJ, Hamid Q. Expression of IL-12 and IL-13 mRNA in asthma and their modulation in response to steroid therapy. Am J Respir Crit Care Med. 1997 Mar;155(3):845–851. [PubMed]
  • van der Pouw Kraan TC, Boeije LC, de Groot ER, Stapel SO, Snijders A, Kapsenberg ML, van der Zee JS, Aarden LA. Reduced production of IL-12 and IL-12-dependent IFN-gamma release in patients with allergic asthma. J Immunol. 1997 Jun 1;158(11):5560–5565. [PubMed]
  • Kips JC, Brusselle GJ, Joos GF, Peleman RA, Tavernier JH, Devos RR, Pauwels RA. Interleukin-12 inhibits antigen-induced airway hyperresponsiveness in mice. Am J Respir Crit Care Med. 1996 Feb;153(2):535–539. [PubMed]
  • Gavett SH, O'Hearn DJ, Li X, Huang SK, Finkelman FD, Wills-Karp M. Interleukin 12 inhibits antigen-induced airway hyperresponsiveness, inflammation, and Th2 cytokine expression in mice. J Exp Med. 1995 Nov 1;182(5):1527–1536. [PMC free article] [PubMed]
  • Bruselle GG, Kips JC, Peleman RA, Joos GF, Devos RR, Tavernier JH, Pauwels RA. Role of IFN-gamma in the inhibition of the allergic airway inflammation caused by IL-12. Am J Respir Cell Mol Biol. 1997 Dec;17(6):767–771. [PubMed]
  • Sur S, Lam J, Bouchard P, Sigounas A, Holbert D, Metzger WJ. Immunomodulatory effects of IL-12 on allergic lung inflammation depend on timing of doses. J Immunol. 1996 Nov 1;157(9):4173–4180. [PubMed]
  • Lee Y, Fu C, Chiang B. Administration of interleukin-12 exerts a therapeutic instead of a long-term preventive effect on mite Der p I allergen-induced animal model of airway inflammation. Immunology. 1999 Jun;97(2):232–240. [PMC free article] [PubMed]
  • Hogan SP, Foster PS, Tan X, Ramsay AJ. Mucosal IL-12 gene delivery inhibits allergic airways disease and restores local antiviral immunity. Eur J Immunol. 1998 Feb;28(2):413–423. [PubMed]
  • Stämpfli MR, Cwiartka M, Gajewska BU, Alvarez D, Ritz SA, Inman MD, Xing Z, Jordana M. Interleukin-10 gene transfer to the airway regulates allergic mucosal sensitization in mice. Am J Respir Cell Mol Biol. 1999 Nov;21(5):586–596. [PubMed]
  • Hofstra CL, Van Ark I, Hofman G, Kool M, Nijkamp FP, Van Oosterhout AJ. Prevention of Th2-like cell responses by coadministration of IL-12 and IL-18 is associated with inhibition of antigen-induced airway hyperresponsiveness, eosinophilia, and serum IgE levels. J Immunol. 1998 Nov 1;161(9):5054–5060. [PubMed]
  • van der Pouw Kraan TC, Boeije LC, de Groot ER, Stapel SO, Snijders A, Kapsenberg ML, van der Zee JS, Aarden LA. Reduced production of IL-12 and IL-12-dependent IFN-gamma release in patients with allergic asthma. J Immunol. 1997 Jun 1;158(11):5560–5565. [PubMed]
  • Blotta MH, DeKruyff RH, Umetsu DT. Corticosteroids inhibit IL-12 production in human monocytes and enhance their capacity to induce IL-4 synthesis in CD4+ lymphocytes. J Immunol. 1997 Jun 15;158(12):5589–5595. [PubMed]
  • van der Pouw Kraan TC, Boeije LC, Smeenk RJ, Wijdenes J, Aarden LA. Prostaglandin-E2 is a potent inhibitor of human interleukin 12 production. J Exp Med. 1995 Feb 1;181(2):775–779. [PMC free article] [PubMed]
  • Panina-Bordignon P, Mazzeo D, Lucia PD, D'Ambrosio D, Lang R, Fabbri L, Self C, Sinigaglia F. Beta2-agonists prevent Th1 development by selective inhibition of interleukin 12. J Clin Invest. 1997 Sep 15;100(6):1513–1519. [PMC free article] [PubMed]

Articles from Mediators of Inflammation are provided here courtesy of Hindawi Publishing Corporation


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...