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J Exp Med. 1991 Dec 1; 174(6): 1549–1555.
PMCID: PMC2119047

Macrophage deactivation by interleukin 10

Abstract

Recombinant mouse interleukin 10 (IL-10) was exceedingly potent at suppressing the ability of mouse peritoneal macrophages (m phi) to release tumor necrosis factor alpha (TNF-alpha). The IC50 of IL-10 for the suppression of TNF-alpha release induced by 0.5 microgram/ml lipopolysaccharide was 0.04 +/- 0.03 U/ml, with as little as 1 U/ml suppressing TNF-alpha production by a factor of 21.4 +/- 2.5. At 10 U/ml, IL-10 markedly suppressed m phi release of reactive oxygen intermediates (ROI) (IC50 3.7 +/- 1.8 U/ml), but only weakly inhibited m phi release of reactive nitrogen intermediates (RNI). Since TNF-alpha is a T cell growth and differentiation factor, whereas ROI and RNI are known to inhibit lymphocyte function, it is possible that m phi exposed to low concentrations of IL-10 suppress lymphocytes. m phi deactivated by higher concentrations of IL-10 might be permissive for the growth of microbial pathogens and tumor cells, as TNF-alpha, ROI, and RNI are major antimicrobial and tumoricidal products of m phi. IL-10's effects on m phi overlap with but are distinct from the effects of the two previously described cytokines that suppress the function of mouse m phi, transforming growth factor beta and macrophage deactivation factor. Based on results with neutralizing antibodies, all three m phi suppressor factors appear to act independently.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • 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, 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]
  • 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]
  • Moore KW, Vieira P, Fiorentino DF, Trounstine ML, Khan TA, Mosmann TR. Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science. 1990 Jun 8;248(4960):1230–1234. [PubMed]
  • Kehrl JH, Wakefield LM, Roberts AB, Jakowlew S, Alvarez-Mon M, Derynck R, Sporn MB, Fauci AS. Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth. J Exp Med. 1986 May 1;163(5):1037–1050. [PMC free article] [PubMed]
  • Wahl SM, Hunt DA, Wong HL, Dougherty S, McCartney-Francis N, Wahl LM, Ellingsworth L, Schmidt JA, Hall G, Roberts AB, et al. Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation. J Immunol. 1988 May 1;140(9):3026–3032. [PubMed]
  • Fiorentino DF, Zlotnik A, Vieira P, Mosmann TR, Howard M, Moore KW, O'Garra A. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol. 1991 May 15;146(10):3444–3451. [PubMed]
  • Nathan CF. Secretory products of macrophages. J Clin Invest. 1987 Feb;79(2):319–326. [PMC free article] [PubMed]
  • Tsunawaki S, Sporn M, Ding A, Nathan C. Deactivation of macrophages by transforming growth factor-beta. Nature. 1988 Jul 21;334(6179):260–262. [PubMed]
  • Silva JS, Twardzik DR, Reed SG. Regulation of Trypanosoma cruzi infections in vitro and in vivo by transforming growth factor beta (TGF-beta). J Exp Med. 1991 Sep 1;174(3):539–545. [PMC free article] [PubMed]
  • Srimal S, Nathan C. Purification of macrophage deactivating factor. J Exp Med. 1990 Apr 1;171(4):1347–1361. [PMC free article] [PubMed]
  • Lehn M, Weiser WY, Engelhorn S, Gillis S, Remold HG. IL-4 inhibits H2O2 production and antileishmanial capacity of human cultured monocytes mediated by IFN-gamma. J Immunol. 1989 Nov 1;143(9):3020–3024. [PubMed]
  • Hart PH, Vitti GF, Burgess DR, Whitty GA, Piccoli DS, Hamilton JA. Potential antiinflammatory effects of interleukin 4: suppression of human monocyte tumor necrosis factor alpha, interleukin 1, and prostaglandin E2. Proc Natl Acad Sci U S A. 1989 May;86(10):3803–3807. [PMC free article] [PubMed]
  • Essner R, Rhoades K, McBride WH, Morton DL, Economou JS. IL-4 down-regulates IL-1 and TNF gene expression in human monocytes. J Immunol. 1989 Jun 1;142(11):3857–3861. [PubMed]
  • Szuro-Sudol A, Nathan CF. Suppression of macrophage oxidative metabolism by products of malignant and nonmalignant cells. J Exp Med. 1982 Oct 1;156(4):945–961. [PMC free article] [PubMed]
  • Szuro-Sudol A, Murray HW, Nathan CF. Suppression of macrophage antimicrobial activity by a tumor cell product. J Immunol. 1983 Jul;131(1):384–387. [PubMed]
  • Tsunawaki S, Sporn M, Nathan C. Comparison of transforming growth factor-beta and a macrophage- deactivating polypeptide from tumor cells. Differences in antigenicity and mechanism of action. J Immunol. 1989 May 15;142(10):3462–3468. [PubMed]
  • Ding A, Nathan CF, Graycar J, Derynck R, Stuehr DJ, Srimal S. Macrophage deactivating factor and transforming growth factors-beta 1 -beta 2 and -beta 3 inhibit induction of macrophage nitrogen oxide synthesis by IFN-gamma. J Immunol. 1990 Aug 1;145(3):940–944. [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]
  • Mosmann TR, Schumacher JH, Fiorentino DF, Leverah J, Moore KW, Bond MW. Isolation of monoclonal antibodies specific for IL-4, IL-5, IL-6, and a new Th2-specific cytokine (IL-10), cytokine synthesis inhibitory factor, by using a solid phase radioimmunoadsorbent assay. J Immunol. 1990 Nov 1;145(9):2938–2945. [PubMed]
  • Ding AH, Nathan CF, Stuehr DJ. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J Immunol. 1988 Oct 1;141(7):2407–2412. [PubMed]
  • Eskandari MK, Nguyen DT, Kunkel SL, Remick DG. WEHI 164 subclone 13 assay for TNF: sensitivity, specificity, and reliability. Immunol Invest. 1990 Feb;19(1):69–79. [PubMed]
  • Stenger S, Solbach W, Röllinghoff M, Bogdan C. Cytokine interactions in experimental cutaneous leishmaniasis. II. Endogenous tumor necrosis factor-alpha production by macrophages is induced by the synergistic action of interferon (IFN)-gamma and interleukin (IL) 4 and accounts for the antiparasitic effect mediated by IFN-gamma and IL 4. Eur J Immunol. 1991 Jul;21(7):1669–1675. [PubMed]
  • Gillis S, Ferm MM, Ou W, Smith KA. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. [PMC free article] [PubMed]
  • Espevik T, Figari IS, Shalaby MR, Lackides GA, Lewis GD, Shepard HM, Palladino MA., Jr Inhibition of cytokine production by cyclosporin A and transforming growth factor beta. J Exp Med. 1987 Aug 1;166(2):571–576. [PMC free article] [PubMed]
  • Nelson BJ, Ralph P, Green SJ, Nacy CA. Differential susceptibility of activated macrophage cytotoxic effector reactions to the suppressive effects of transforming growth factor-beta 1. J Immunol. 1991 Mar 15;146(6):1849–1857. [PubMed]
  • Scheurich P, Thoma B, Ucer U, Pfizenmaier K. Immunoregulatory activity of recombinant human tumor necrosis factor (TNF)-alpha: induction of TNF receptors on human T cells and TNF-alpha-mediated enhancement of T cell responses. J Immunol. 1987 Mar 15;138(6):1786–1790. [PubMed]
  • Ranges GE, Zlotnik A, Espevik T, Dinarello CA, Cerami A, Palladino MA., Jr Tumor necrosis factor alpha/cachectin is a growth factor for thymocytes. Synergistic interactions with other cytokines. J Exp Med. 1988 Apr 1;167(4):1472–1478. [PMC free article] [PubMed]
  • Yokota S, Geppert TD, Lipsky PE. Enhancement of antigen- and mitogen-induced human T lymphocyte proliferation by tumor necrosis factor-alpha. J Immunol. 1988 Jan 15;140(2):531–536. [PubMed]
  • Metzger Z, Hoffeld JT, Oppenheim JJ. Macrophage-mediated suppression. I. Evidence for participation of both hdyrogen peroxide and prostaglandins in suppression of murine lymphocyte proliferation. J Immunol. 1980 Feb;124(2):983–988. [PubMed]
  • Hoffman RA, Langrehr JM, Billiar TR, Curran RD, Simmons RL. Alloantigen-induced activation of rat splenocytes is regulated by the oxidative metabolism of L-arginine. J Immunol. 1990 Oct 1;145(7):2220–2226. [PubMed]
  • Mills CD. Molecular basis of "suppressor" macrophages. Arginine metabolism via the nitric oxide synthetase pathway. J Immunol. 1991 Apr 15;146(8):2719–2723. [PubMed]
  • Green SJ, Crawford RM, Hockmeyer JT, Meltzer MS, Nacy CA. Leishmania major amastigotes initiate the L-arginine-dependent killing mechanism in IFN-gamma-stimulated macrophages by induction of tumor necrosis factor-alpha. J Immunol. 1990 Dec 15;145(12):4290–4297. [PubMed]
  • Drapier JC, Wietzerbin J, Hibbs JB., Jr Interferon-gamma and tumor necrosis factor induce the L-arginine-dependent cytotoxic effector mechanism in murine macrophages. Eur J Immunol. 1988 Oct;18(10):1587–1592. [PubMed]
  • Nathan CF, Hibbs JB., Jr Role of nitric oxide synthesis in macrophage antimicrobial activity. Curr Opin Immunol. 1991 Feb;3(1):65–70. [PubMed]
  • MacNeil IA, Suda T, Moore KW, Mosmann TR, Zlotnik A. IL-10, a novel growth cofactor for mature and immature T cells. J Immunol. 1990 Dec 15;145(12):4167–4173. [PubMed]

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