• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of annrheumdAnnals of the Rheumatic DiseasesCurrent TOCInstructions for authors
Ann Rheum Dis. Nov 1999; 58(Suppl 1): I107–I113.
PMCID: PMC1766578

Immunomodulation by thalidomide and thalidomide analogues

Full Text

The Full Text of this article is available as a PDF (97K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Elkon KB, Liu CC, Gall JG, Trevejo J, Marino MW, Abrahamsen KA, Song X, Zhou JL, Old LJ, Crystal RG, et al. Tumor necrosis factor alpha plays a central role in immune-mediated clearance of adenoviral vectors. Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9814–9819. [PMC free article] [PubMed]
  • Nashleanas M, Kanaly S, Scott P. Control of Leishmania major infection in mice lacking TNF receptors. J Immunol. 1998 Jun 1;160(11):5506–5513. [PubMed]
  • O'Brien DP, Briles DE, Szalai AJ, Tu AH, Sanz I, Nahm MH. Tumor necrosis factor alpha receptor I is important for survival from Streptococcus pneumoniae infections. Infect Immun. 1999 Feb;67(2):595–601. [PMC free article] [PubMed]
  • Flynn JL, Goldstein MM, Chan J, Triebold KJ, Pfeffer K, Lowenstein CJ, Schreiber R, Mak TW, Bloom BR. Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice. Immunity. 1995 Jun;2(6):561–572. [PubMed]
  • Kindler V, Sappino AP, Grau GE, Piguet PF, Vassalli P. The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection. Cell. 1989 Mar 10;56(5):731–740. [PubMed]
  • Waage A, Steinshamn S. Cytokine mediators of septic infections in the normal and granulocytopenic host. Eur J Haematol. 1993 May;50(5):243–249. [PubMed]
  • Tracey KJ, Cerami A. Tumor necrosis factor and regulation of metabolism in infection: role of systemic versus tissue levels. Proc Soc Exp Biol Med. 1992 Jun;200(2):233–239. [PubMed]
  • Maini RN, Elliott MJ, Brennan FM, Feldmann M. Beneficial effects of tumour necrosis factor-alpha (TNF-alpha) blockade in rheumatoid arthritis (RA) Clin Exp Immunol. 1995 Aug;101(2):207–212. [PMC free article] [PubMed]
  • Hawkey CJ, Stack WA. Chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. N Engl J Med. 1998 Jan 29;338(5):333–334. [PubMed]
  • Baert FJ, D'Haens GR, Peeters M, Hiele MI, Schaible TF, Shealy D, Geboes K, Rutgeerts PJ. Tumor necrosis factor alpha antibody (infliximab) therapy profoundly down-regulates the inflammation in Crohn's ileocolitis. Gastroenterology. 1999 Jan;116(1):22–28. [PubMed]
  • Sampaio EP, Kaplan G, Miranda A, Nery JA, Miguel CP, Viana SM, Sarno EN. The influence of thalidomide on the clinical and immunologic manifestation of erythema nodosum leprosum. J Infect Dis. 1993 Aug;168(2):408–414. [PubMed]
  • Tramontana JM, Utaipat U, Molloy A, Akarasewi P, Burroughs M, Makonkawkeyoon S, Johnson B, Klausner JD, Rom W, Kaplan G. Thalidomide treatment reduces tumor necrosis factor alpha production and enhances weight gain in patients with pulmonary tuberculosis. Mol Med. 1995 May;1(4):384–397. [PMC free article] [PubMed]
  • Tsenova L, Sokol K, Freedman VH, Kaplan G. A combination of thalidomide plus antibiotics protects rabbits from mycobacterial meningitis-associated death. J Infect Dis. 1998 Jun;177(6):1563–1572. [PubMed]
  • Moreira AL, Wang J, Sarno EN, Kaplan G. Thalidomide protects mice against LPS-induced shock. Braz J Med Biol Res. 1997 Oct;30(10):1199–1207. [PubMed]
  • Sampaio EP, Sarno EN, Galilly R, Cohn ZA, Kaplan G. Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes. J Exp Med. 1991 Mar 1;173(3):699–703. [PMC free article] [PubMed]
  • Corral LG, Muller GW, Moreira AL, Chen Y, Wu M, Stirling D, Kaplan G. Selection of novel analogs of thalidomide with enhanced tumor necrosis factor alpha inhibitory activity. Mol Med. 1996 Jul;2(4):506–515. [PMC free article] [PubMed]
  • Moreira AL, Sampaio EP, Zmuidzinas A, Frindt P, Smith KA, Kaplan G. Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation. J Exp Med. 1993 Jun 1;177(6):1675–1680. [PMC free article] [PubMed]
  • Moreira AL, Corral LG, Ye W, Johnson B, Stirling D, Muller GW, Freedman VH, Kaplan G. Thalidomide and thalidomide analogs reduce HIV type 1 replication in human macrophages in vitro. AIDS Res Hum Retroviruses. 1997 Jul 1;13(10):857–863. [PubMed]
  • Marriott JB, Westby M, Cookson S, Guckian M, Goodbourn S, Muller G, Shire MG, Stirling D, Dalgleish AG. CC-3052: a water-soluble analog of thalidomide and potent inhibitor of activation-induced TNF-alpha production. J Immunol. 1998 Oct 15;161(8):4236–4243. [PubMed]
  • Müller JM, Ziegler-Heitbrock HW, Baeuerle PA. Nuclear factor kappa B, a mediator of lipopolysaccharide effects. Immunobiology. 1993 Apr;187(3-5):233–256. [PubMed]
  • Bachelerie F, Alcami J, Arenzana-Seisdedos F, Virelizier JL. HIV enhancer activity perpetuated by NF-kappa B induction on infection of monocytes. Nature. 1991 Apr 25;350(6320):709–712. [PubMed]
  • Haslett PA, Corral LG, Albert M, Kaplan G. Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset. J Exp Med. 1998 Jun 1;187(11):1885–1892. [PMC free article] [PubMed]
  • Mueller DL, Jenkins MK, Schwartz RH. Clonal expansion versus functional clonal inactivation: a costimulatory signalling pathway determines the outcome of T cell antigen receptor occupancy. Annu Rev Immunol. 1989;7:445–480. [PubMed]
  • Corral LG, Haslett PA, Muller GW, Chen R, Wong LM, Ocampo CJ, Patterson RT, Stirling DI, Kaplan G. Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha. J Immunol. 1999 Jul 1;163(1):380–386. [PubMed]
  • Haslett PA, Klausner JD, Makonkawkeyoon S, Moreira A, Metatratip P, Boyle B, Kunachiwa W, Maneekarn N, Vongchan P, Corral LG, et al. Thalidomide stimulates T cell responses and interleukin 12 production in HIV-infected patients. AIDS Res Hum Retroviruses. 1999 Sep 1;15(13):1169–1179. [PubMed]
  • Ranheim EA, Kipps TJ. Activated T cells induce expression of B7/BB1 on normal or leukemic B cells through a CD40-dependent signal. J Exp Med. 1993 Apr 1;177(4):925–935. [PMC free article] [PubMed]
  • DeKruyff RH, Gieni RS, Umetsu DT. Antigen-driven but not lipopolysaccharide-driven IL-12 production in macrophages requires triggering of CD40. J Immunol. 1997 Jan 1;158(1):359–366. [PubMed]
  • Hollenbaugh D, Ochs HD, Noelle RJ, Ledbetter JA, Aruffo A. The role of CD40 and its ligand in the regulation of the immune response. Immunol Rev. 1994 Apr;138:23–37. [PubMed]
  • Buhlmann JE, Gonzalez M, Ginther B, Panoskaltsis-Mortari A, Blazar BR, Greiner DL, Rossini AA, Flavell R, Noelle RJ. Cutting edge: sustained expansion of CD8+ T cells requires CD154 expression by Th cells in acute graft versus host disease. J Immunol. 1999 Apr 15;162(8):4373–4376. [PubMed]
  • Klausner JD, Makonkawkeyoon S, Akarasewi P, Nakata K, Kasinrerk W, Corral L, Dewar RL, Lane HC, Freedman VH, Kaplan G. The effect of thalidomide on the pathogenesis of human immunodeficiency virus type 1 and M. tuberculosis infection. J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Mar 1;11(3):247–257. [PubMed]
  • Schuler U, Ehninger G. Thalidomide: rationale for renewed use in immunological disorders. Drug Saf. 1995 Jun;12(6):364–369. [PubMed]
  • Jacobson JM, Greenspan JS, Spritzler J, Ketter N, Fahey JL, Jackson JB, Fox L, Chernoff M, Wu AW, MacPhail LA, et al. Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med. 1997 May 22;336(21):1487–1493. [PubMed]
  • Vogelsang GB, Farmer ER, Hess AD, Altamonte V, Beschorner WE, Jabs DA, Corio RL, Levin LS, Colvin OM, Wingard JR, et al. Thalidomide for the treatment of chronic graft-versus-host disease. N Engl J Med. 1992 Apr 16;326(16):1055–1058. [PubMed]
  • Castilla EE, Ashton-Prolla P, Barreda-Mejia E, Brunoni D, Cavalcanti DP, Correa-Neto J, Delgadillo JL, Dutra MG, Felix T, Giraldo A, et al. Thalidomide, a current teratogen in South America. Teratology. 1996 Dec;54(6):273–277. [PubMed]
  • Tseng S, Pak G, Washenik K, Pomeranz MK, Shupack JL. Rediscovering thalidomide: a review of its mechanism of action, side effects, and potential uses. J Am Acad Dermatol. 1996 Dec;35(6):969–979. [PubMed]
  • Günzler V. Thalidomide in human immunodeficiency virus (HIV) patients. A review of safety considerations. Drug Saf. 1992 Mar-Apr;7(2):116–134. [PubMed]
  • Muller GW, Corral LG, Shire MG, Wang H, Moreira A, Kaplan G, Stirling DI. Structural modifications of thalidomide produce analogs with enhanced tumor necrosis factor inhibitory activity. J Med Chem. 1996 Aug 16;39(17):3238–3240. [PubMed]
  • Muller GW, Shire MG, Wong LM, Corral LG, Patterson RT, Chen Y, Stirling DI. Thalidomide analogs and PDE4 inhibition. Bioorg Med Chem Lett. 1998 Oct 6;8(19):2669–2674. [PubMed]
  • Muller GW, Chen R, Huang SY, Corral LG, Wong LM, Patterson RT, Chen Y, Kaplan G, Stirling DI. Amino-substituted thalidomide analogs: potent inhibitors of TNF-alpha production. Bioorg Med Chem Lett. 1999 Jun 7;9(11):1625–1630. [PubMed]
  • Verghese MW, McConnell RT, Lenhard JM, Hamacher L, Jin SL. Regulation of distinct cyclic AMP-specific phosphodiesterase (phosphodiesterase type 4) isozymes in human monocytic cells. Mol Pharmacol. 1995 Jun;47(6):1164–1171. [PubMed]
  • Verghese MW, McConnell RT, Strickland AB, Gooding RC, Stimpson SA, Yarnall DP, Taylor JD, Furdon PJ. Differential regulation of human monocyte-derived TNF alpha and IL-1 beta by type IV cAMP-phosphodiesterase (cAMP-PDE) inhibitors. J Pharmacol Exp Ther. 1995 Mar;272(3):1313–1320. [PubMed]
  • Gantner F, Küsters S, Wendel A, Hatzelmann A, Schudt C, Tiegs G. Protection from T cell-mediated murine liver failure by phosphodiesterase inhibitors. J Pharmacol Exp Ther. 1997 Jan;280(1):53–60. [PubMed]
  • Tamir A, Granot Y, Isakov N. Inhibition of T lymphocyte activation by cAMP is associated with down-regulation of two parallel mitogen-activated protein kinase pathways, the extracellular signal-related kinase and c-Jun N-terminal kinase. J Immunol. 1996 Aug 15;157(4):1514–1522. [PubMed]
  • Moller DR, Wysocka M, Greenlee BM, Ma X, Wahl L, Flockhart DA, Trinchieri G, Karp CL. Inhibition of IL-12 production by thalidomide. J Immunol. 1997 Nov 15;159(10):5157–5161. [PubMed]
  • Takenaka H, Maruo S, Yamamoto N, Wysocka M, Ono S, Kobayashi M, Yagita H, Okumura K, Hamaoka T, Trinchieri G, et al. Regulation of T cell-dependent and -independent IL-12 production by the three Th2-type cytokines IL-10, IL-6, and IL-4. J Leukoc Biol. 1997 Jan;61(1):80–87. [PubMed]
  • Hamuryudan V, Mat C, Saip S, Ozyazgan Y, Siva A, Yurdakul S, Zwingenberger K, Yazici H. Thalidomide in the treatment of the mucocutaneous lesions of the Behçet syndrome. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1998 Mar 15;128(6):443–450. [PubMed]
  • Chao NJ, Parker PM, Niland JC, Wong RM, Dagis A, Long GD, Nademanee AP, Negrin RS, Snyder DS, Hu WW, et al. Paradoxical effect of thalidomide prophylaxis on chronic graft-vs.-host disease. Biol Blood Marrow Transplant. 1996 May;2(2):86–92. [PubMed]
  • Wolkenstein P, Latarjet J, Roujeau JC, Duguet C, Boudeau S, Vaillant L, Maignan M, Schuhmacher MH, Milpied B, Pilorget A, et al. Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis. Lancet. 1998 Nov 14;352(9140):1586–1589. [PubMed]
  • Harbinson PL, MacLeod D, Hawksworth R, O'Toole S, Sullivan PJ, Heath P, Kilfeather S, Page CP, Costello J, Holgate ST, et al. The effect of a novel orally active selective PDE4 isoenzyme inhibitor (CDP840) on allergen-induced responses in asthmatic subjects. Eur Respir J. 1997 May;10(5):1008–1014. [PubMed]
  • Hanifin JM, Chan SC, Cheng JB, Tofte SJ, Henderson WR, Jr, Kirby DS, Weiner ES. Type 4 phosphodiesterase inhibitors have clinical and in vitro anti-inflammatory effects in atopic dermatitis. J Invest Dermatol. 1996 Jul;107(1):51–56. [PubMed]
  • Sekut L, Yarnall D, Stimpson SA, Noel LS, Bateman-Fite R, Clark RL, Brackeen MF, Menius JA, Jr, Connolly KM. Anti-inflammatory activity of phosphodiesterase (PDE)-IV inhibitors in acute and chronic models of inflammation. Clin Exp Immunol. 1995 Apr;100(1):126–132. [PMC free article] [PubMed]
  • Torphy TJ. Phosphodiesterase isozymes: molecular targets for novel antiasthma agents. Am J Respir Crit Care Med. 1998 Feb;157(2):351–370. [PubMed]
  • Carpenter DO, Briggs DB, Knox AP, Strominger N. Excitation of area postrema neurons by transmitters, peptides, and cyclic nucleotides. J Neurophysiol. 1988 Feb;59(2):358–369. [PubMed]
  • Chirmule N, McCloskey TW, Hu R, Kalyanaraman VS, Pahwa S. HIV gp120 inhibits T cell activation by interfering with expression of costimulatory molecules CD40 ligand and CD80 (B71). J Immunol. 1995 Jul 15;155(2):917–924. [PubMed]
  • Chehimi J, Starr SE, Frank I, D'Andrea A, Ma X, MacGregor RR, Sennelier J, Trinchieri G. Impaired interleukin 12 production in human immunodeficiency virus-infected patients. J Exp Med. 1994 Apr 1;179(4):1361–1366. [PMC free article] [PubMed]
  • Clerici M, Lucey DR, Berzofsky JA, Pinto LA, Wynn TA, Blatt SP, Dolan MJ, Hendrix CW, Wolf SF, Shearer GM. Restoration of HIV-specific cell-mediated immune responses by interleukin-12 in vitro. Science. 1993 Dec 10;262(5140):1721–1724. [PubMed]
  • Wilson CC, Olson WC, Tuting T, Rinaldo CR, Lotze MT, Storkus WJ. HIV-1-specific CTL responses primed in vitro by blood-derived dendritic cells and Th1-biasing cytokines. J Immunol. 1999 Mar 1;162(5):3070–3078. [PubMed]
  • Belyakov IM, Ahlers JD, Brandwein BY, Earl P, Kelsall BL, Moss B, Strober W, Berzofsky JA. The importance of local mucosal HIV-specific CD8(+) cytotoxic T lymphocytes for resistance to mucosal viral transmission in mice and enhancement of resistance by local administration of IL-12. J Clin Invest. 1998 Dec 15;102(12):2072–2081. [PMC free article] [PubMed]
  • Chougnet C, Thomas E, Landay AL, Kessler HA, Buchbinder S, Scheer S, Shearer GM. CD40 ligand and IFN-gamma synergistically restore IL-12 production in HIV-infected patients. Eur J Immunol. 1998 Feb;28(2):646–656. [PubMed]
  • Nakajima A, Kodama T, Morimoto S, Azuma M, Takeda K, Oshima H, Yoshino S, Yagita H, Okumura K. Antitumor effect of CD40 ligand: elicitation of local and systemic antitumor responses by IL-12 and B7. J Immunol. 1998 Aug 15;161(4):1901–1907. [PubMed]
  • Brunda MJ, Luistro L, Warrier RR, Wright RB, Hubbard BR, Murphy M, Wolf SF, Gately MK. Antitumor and antimetastatic activity of interleukin 12 against murine tumors. J Exp Med. 1993 Oct 1;178(4):1223–1230. [PMC free article] [PubMed]
  • Coughlin CM, Salhany KE, Wysocka M, Aruga E, Kurzawa H, Chang AE, Hunter CA, Fox JC, Trinchieri G, Lee WM. Interleukin-12 and interleukin-18 synergistically induce murine tumor regression which involves inhibition of angiogenesis. J Clin Invest. 1998 Mar 15;101(6):1441–1452. [PMC free article] [PubMed]
  • Bauer KS, Dixon SC, Figg WD. Inhibition of angiogenesis by thalidomide requires metabolic activation, which is species-dependent. Biochem Pharmacol. 1998 Jun 1;55(11):1827–1834. [PubMed]
  • Kenyon BM, Browne F, D'Amato RJ. Effects of thalidomide and related metabolites in a mouse corneal model of neovascularization. Exp Eye Res. 1997 Jun;64(6):971–978. [PubMed]
  • Joseph IB, Isaacs JT. Macrophage role in the anti-prostate cancer response to one class of antiangiogenic agents. J Natl Cancer Inst. 1998 Nov 4;90(21):1648–1653. [PubMed]
  • D'Amato RJ, Loughnan MS, Flynn E, Folkman J. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):4082–4085. [PMC free article] [PubMed]
  • Berenson JR, Bergsagel PL, Munshi N. Initiation and maintenance of multiple myeloma. Semin Hematol. 1999 Jan;36(1 Suppl 3):9–13. [PubMed]
  • Posavad CM, Koelle DM, Corey L. High frequency of CD8+ cytotoxic T-lymphocyte precursors specific for herpes simplex viruses in persons with genital herpes. J Virol. 1996 Nov;70(11):8165–8168. [PMC free article] [PubMed]
  • Ferbas J. Perspectives on the role of CD8+ cell suppressor factors and cytotoxic T lymphocytes during HIV infection. AIDS Res Hum Retroviruses. 1998 Jun;14 (Suppl 2):S153–S160. [PubMed]
  • Gollob JA, Schnipper CP, Orsini E, Murphy E, Daley JF, Lazo SB, Frank DA, Neuberg D, Ritz J. Characterization of a novel subset of CD8(+) T cells that expands in patients receiving interleukin-12. J Clin Invest. 1998 Aug 1;102(3):561–575. [PMC free article] [PubMed]
  • Cavanagh LL, Barnetson RS, Basten A, Halliday GM. Dendritic epidermal T-cell involvement in induction of CD8+ T cell-mediated immunity against an ultraviolet radiation-induced skin tumor. Int J Cancer. 1997 Jan 6;70(1):98–105. [PubMed]
  • Odeka EB, Miller V. Thalidomide in oral Crohn's disease refractory to conventional medical treatment. J Pediatr Gastroenterol Nutr. 1997 Aug;25(2):250–251. [PubMed]
  • Waters MF, Laing AB, Ambikapathy A, Lennard-Jones JE. Treatment of ulcerative colitis with thalidomide. Br Med J. 1979 Mar 24;1(6166):792–792. [PMC free article] [PubMed]
  • Wettstein AR, Meagher AP. Thalidomide in Crohn's disease. Lancet. 1997 Nov 15;350(9089):1445–1446. [PubMed]
  • Stack WA, Mann SD, Roy AJ, Heath P, Sopwith M, Freeman J, Holmes G, Long R, Forbes A, Kamm MA. Randomised controlled trial of CDP571 antibody to tumour necrosis factor-alpha in Crohn's disease. Lancet. 1997 Feb 22;349(9051):521–524. [PubMed]
  • Mayer L, Eisenhardt D. Lack of induction of suppressor T cells by intestinal epithelial cells from patients with inflammatory bowel disease. J Clin Invest. 1990 Oct;86(4):1255–1260. [PMC free article] [PubMed]

Figures and Tables

Figure 1
Chemical structures of thalidomide and selected thalidomide analogues.

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Group

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...