Skip to main content
Log in

Thalidomide: Rationale for Renewed Use in Immunological Disorders

  • Leading Article
  • Published:
Drug Safety Aims and scope Submit manuscript

Summary

Despite its inherent teratogenic risk, thalidomide has over the years proven to be of clinical use in a small number of mainly immunological diseases (e.g. erythema nodosum leprosum, Behcet’s syndrome and rheumatoid arthritis). The mode of action of thalidomide is still poorly understood. Recent research has shown a decrease in tumour necrosis factorα (TNFα) during thalidomide treatment in several settings. Others have found altered expression of adhesion molecules. Currently, the most interesting new fields of application are the prevention and treatment of graft-versus-host disease in allogeneic bone marrow transplantation and the treatment of aphthous ulceration in HIV-positive patients. Contraceptive measures must be instituted in women receiving thalidomide, and careful monitoring for neurological adverse effects is required in all patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Roath S, Elves MW, Israels MCG. Effects of thalidomide and its derivatives on human leucocytes cultured in vitro. Lancet 1963; 1: 249–50

    Article  PubMed  CAS  Google Scholar 

  2. Field EO, Gibbs JE, Tucker DF, et al. Effect of thalidomide on the graft versus host reaction. Nature 1966; 211: 1308–10

    Article  PubMed  CAS  Google Scholar 

  3. Another chance for thalidomide? Lancet 1965; 2: 1059

  4. Sheskin J. Thalidomide in the treatment of lepra reactions. Clin Pharmacol Ther 1965; 6: 303–6

    PubMed  CAS  Google Scholar 

  5. Lehner T, Sullivan FM. Thalidomide, orogenital ulcers, and the risk of teratogenesis [letter]. Lancet 1985; 1: 288–9

    Article  PubMed  CAS  Google Scholar 

  6. Crawford CL. Use of thalidomide in leprosy. BMJ 1991; 302: 1603–4

    Article  PubMed  CAS  Google Scholar 

  7. Jones GR. Thalidomide: 35 years on and still deforming. Lancet 1994; 343: 1041

    Article  PubMed  CAS  Google Scholar 

  8. Hawkins DF. Thalidomide for systemic lupus erythematosus. Lancet 1992; 339: 1057

    Article  PubMed  CAS  Google Scholar 

  9. Crawford CL. Thalidomide neuropathy. N Engl J Med 1992; 327: 735

    PubMed  CAS  Google Scholar 

  10. Barnhill RL, McDougall AC. Thalidomide: use and possible mode of action in reactional lepromatous leprosy and in various other conditions. J Am Acad Dermatol 1982; 7: 317–23

    Article  PubMed  CAS  Google Scholar 

  11. Stephens TD. Proposed mechanisms of action in thalidomide embryopathy. Teratology 1988; 38: 229–39

    Article  PubMed  CAS  Google Scholar 

  12. Wood PM, Proctor SJ. The potential use of thalidomide in the therapy of graft-versus-host disease: a review of clinical and laboratory information. Leuk Res 1990; 14: 395–9

    Article  PubMed  CAS  Google Scholar 

  13. Gunzler V. Thalidomide in human immunodeficiency virus (HIV) patients. A review of safety considerations. Drug Saf 1992; 7: 116–34

    Article  PubMed  CAS  Google Scholar 

  14. Bore PJ, Scothorne RJ. Effect of thalidomide on survival of skin homografts in rabbits. Lancet 1966; 1: 1240–1

    Article  PubMed  CAS  Google Scholar 

  15. Vogelsang GB, Hess AD, Gordon G, et al. Treatment and prevention of acute graft-versus-host disease with thalidomide in a rat model. Transplantation 1986; 41: 644–7

    Article  PubMed  CAS  Google Scholar 

  16. Heney D, Lewis IJ, Bailey CC. Thalidomide for chronic graft-versus-host disease in children. Lancet 1988; 2: 1317

    Article  PubMed  CAS  Google Scholar 

  17. McCarthy DM, Kanfer EJ, Barrett AJ. Thalidomide for the therapy of graft-versus-host disease following allogeneic bone marrow transplantation. Biomed Pharmacother 1989; 43: 693–7

    Article  PubMed  CAS  Google Scholar 

  18. Lopez J, Ulibarrena C, Garcia-Larana J, et al. Thalidomide as therapy for intestinal chronic GVHD. Bone Marrow Transplant 1993; 11: 251–2

    PubMed  CAS  Google Scholar 

  19. Vogelsang GB, Farmer ER, Hess AD, et al. Thalidomide for the treatment of chronic graft-versus-host disease. N Engl J Med 1992; 326: 1055–8

    Article  PubMed  CAS  Google Scholar 

  20. Heney D, Norfolk DR, Wheeldon J, et al. Thalidomide treatment for chronic graft-versus-host disease. Br J Haematol 1991; 78: 23–7

    Article  PubMed  CAS  Google Scholar 

  21. Tamura F, Vogelsang GB, Reitz BA, et al. Combination thalidomide and cyclosporine for cardiac allograft rejection. Comparison with combination methylprednisolone and cyclosporine. Transplantation 1990; 49: 20–5

    Article  PubMed  CAS  Google Scholar 

  22. Ostraat O, Ekberg H, Schatz H, et al. Thalidomide prolongs graft survival in rat cardiac transplants. Transplant Proc 1992; 24: 2624–5

    PubMed  CAS  Google Scholar 

  23. Emre S, Sumrani N, Hong J. Beneficial effect of thalidomide and ciclosporin combination in heterotopic cardiac transplantation in rats. Eur Surg Res 1990; 22: 336–9

    Article  PubMed  CAS  Google Scholar 

  24. Billingham RE. The feasibility of altering the immunogenicity of grafts. J Invest Dermatol 1976; 67: 149–59

    Article  PubMed  CAS  Google Scholar 

  25. Jorizzo JL, Schmalstieg FC, Solomon ARJ, et al. Thalidomide effects in Behcet’s syndrome and pustular vasculitis. Arch Intern Med 1986; 146: 878–81

    Article  PubMed  CAS  Google Scholar 

  26. Hamza MH. Treatment of Behcet’s disease with thalidomide. Clin Rheumatol 1986; 5: 365–71

    Article  PubMed  CAS  Google Scholar 

  27. Nicolau DP, West TE. Thalidomide: treatment of severe recurrent aphthous stomatitis in patients with AIDS. DICP 1990; 24: 1054–6

    PubMed  CAS  Google Scholar 

  28. Revuz J, Guillaume JC, Janier M, et al. Crossover study of thalidomide vs placebo in severe recurrent aphthous stomatitis. Arch Dermatol 1990; 126: 923–7

    Article  PubMed  CAS  Google Scholar 

  29. Youle M, Clarbour J, Farthing C, et al. Treatment of resistant aphthous ulceration with thalidomide in patients positive for HIV antibody. BMJ 1989; 298: 432

    Article  PubMed  CAS  Google Scholar 

  30. Makonkawkeyoon S, Limson-Pobre RN, Moreira AL, et al. Thalidomide inhibits the replication of human immunodeficiency virus type 1. Proc Natl Acad Sci USA 1993; 90: 5974–8

    Article  PubMed  CAS  Google Scholar 

  31. Silva SR, Viana PC, Lugon NV, et al. Thalidomide for the treatment of uremic pruritus: a crossover randomized double-blind trial. Nephron 1994; 67: 270–3

    Article  PubMed  CAS  Google Scholar 

  32. Hatful SJ, Fester ED, de-Beer DP, et al. Induction of morphological differentiation in the human leukemic cell line K562 by exposure to thalidomide metabolites. Leuk Res 1991; 15: 129–36

    Article  Google Scholar 

  33. Bensaid P, Machet L, Vaillant L, et al. Langerhan’s cell histiocytosis in the adult: regressive parotid involvement following thalidomide therapy. Ann Dermatol Venereol 1992; 119: 281–3

    PubMed  CAS  Google Scholar 

  34. Thomas L, Ducros B, Secchi T, et al. Successful treatment of adult’s Langerhan’s cell histiocytosis with thalidomide. Report of two cases and literature review. Arch Dermatol 1993; 129: 1261–4

    Article  PubMed  CAS  Google Scholar 

  35. Shannon EJ, Miranda RO, Morales MJ, et al. Inhibition of de novo IgM antibody synthesis by thalidomide as a relevant mechanism of action in leprosy. Scand J Immunol 1981; 13: 553–62

    Article  PubMed  CAS  Google Scholar 

  36. Crain E, Mclntosh KR, Gordon G, et al. The effect of thalidomide on experimental autoimmune myasthenia gravis. J Autoimmun 1989; 2: 197–202

    Article  PubMed  CAS  Google Scholar 

  37. Faure M, Thivolet J, Gaucherand M. Inhibition of PMN leukocytes chemotaxis by thalidomide. Arch Dermatol Res 1980; 269: 275–80

    Article  PubMed  CAS  Google Scholar 

  38. Nielsen H, Valerius NH. Thalidomide enhances Superoxide an-ion release from human polymorphonuclear and mononuclear leukocytes. APMIS 1986; 94: 233–7

    CAS  Google Scholar 

  39. Miyachi Y, Ozaki M, Uchida K, et al. Effects of thalidomide on the generation of oxygen intermediates by zymosan-stimulated normal polymorphonuclear leukocytes. Arch Dermatol Res 1982; 274: 363–7

    Article  PubMed  CAS  Google Scholar 

  40. Shannon EJ, Ejigu M, Haile-Mariam HS, et al. Thalidomide’s effectiveness in erythema nodosum leprosum is associated with a decrease in CD4+ cells in the peripheral blood. Lepr Rev 1992; 63: 5–11

    PubMed  CAS  Google Scholar 

  41. Bernai JE, Duran MM, Londono F, et al. Cellular immune effects of thalidomide in actinic prurigo. Int J Dermatol 1992; 31: 599–600

    Article  Google Scholar 

  42. Neubert R, Nogueira AC, Neubert D. Thalidomide derivatives and the immune system. I. Changes in the pattern of integrin receptors and other surface markers on T lymphocyte sub-populations of marmoset blood. Arch Toxicol 1993; 67: 1–17

    Article  PubMed  CAS  Google Scholar 

  43. Neubert R, Nogueira AC, Neubert D. Thalidomide and the immune system. 2. Changes in receptors on blood cells of a healthy volunteer. Life Sci.1992; 51: 2107–16

    Article  PubMed  CAS  Google Scholar 

  44. Sampaio EP, Moreira AL, Sarno EN, et al. Prolonged treatment with recombinant interferon gamma induces erythema nodosum leprosum in lepromatous leprosy patients. J Exp Med 1992; 175: 1729–37

    Article  PubMed  CAS  Google Scholar 

  45. Sampaio EP, Kaplan G, Miranda A, et al. The influence of thalidomide on the clinical and immunologic manifestation of erythema nodosum leprosum. J Infect Dis 1993; 168: 408–14

    Article  PubMed  CAS  Google Scholar 

  46. Barnes PF, Chatterjee D, Brennan PJ, et al. Tumor necrosis factor production in patients with leprosy. Infect Immun 1992; 60: 1441–6

    PubMed  CAS  Google Scholar 

  47. Sampaio EP, Sarno EN, Galilly R, et al. Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes. J Exp Med 1991; 173: 699–703

    Article  PubMed  CAS  Google Scholar 

  48. Moreira AL, Sampaio EP, Zmuidzinas A, et al. Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation. J Exp Med 1993; 177: 1675–80

    Article  PubMed  CAS  Google Scholar 

  49. Weglicki WB, Stafford RE, Dickens BF, et al. Inhibition of tumor necrosis factor-alpha by thalidomide in magnesium deficiency. Mol Cell Biochem 1993; 129: 195–200

    Article  PubMed  CAS  Google Scholar 

  50. Nishimura K, Hashimoto Y, Iwasaki S. Enhancement of phorbolester-induced production of tumor necrosis factor alpha by thalidomide. Biochem Biophys Res Commun 1994; 199: 455–60

    Article  PubMed  CAS  Google Scholar 

  51. Sullivan L, Sano S, Pirmez C. Expression of adhesion molecules in leprosy lesions. Infect Immun 1991; 59: 4154–60

    PubMed  CAS  Google Scholar 

  52. Springer TA. Adhesion receptors of the immune system. Nature 1990; 346: 425–34

    Article  PubMed  CAS  Google Scholar 

  53. Knoche B, Blaschke G. Investigation on the in vitro racemization of thalidomide by high-performance liquid chromatography. J Chromatogr 1994; 666: 235–40

    Article  CAS  Google Scholar 

  54. Gordon GB, Spielberg SP, Blake DA, et al. Thalidomide teratogenesis: evidence for a toxic arene oxide metabolite. Proc Natl Acad Sci U S A 1981; 78: 2545–8

    Article  PubMed  CAS  Google Scholar 

  55. Czejka MJ, Koch HP. Determination of thalidomide and its major metabolites by high-performance liquid chromatography. J Chromatogr 1987; 413: 181–7

    Article  PubMed  CAS  Google Scholar 

  56. Krenn M, Gamcsik MP, Vogelsang GB, et al. Improvements in solubility and stability of thalidomide upon complexation with hydroxypropyl-beta-cyclodextrin. J Pharm Sci 1992; 81: 685–9

    Article  PubMed  CAS  Google Scholar 

  57. Eriksson T, Bjorkman S, Fyge A, et al. Determination of thalidomide in plasma and blood by high-performance liquid chromatography: avoiding hydrolytic degradation. J Chromatogr 1992; 582: 211–6

    Article  PubMed  CAS  Google Scholar 

  58. Ochonisky S, Verroust J, Bastuji-Garin S, et al. Thalidomide neuropathy incidence and clinico-electrophysiologic findings in 42 patients. Arch Dermatol 1994; 130: 66–9

    Article  PubMed  CAS  Google Scholar 

  59. Gutierrez-Rodriguez O, Starusta-Bacal P, Gutierrez-Montes O Thalidomide-induced neuropathy in rheumatoid arthritis patients. Arthritis Rheum 1988; 31: 145–6

    Article  PubMed  CAS  Google Scholar 

  60. Wulff CH, Hoyer H, Asboe-Hansen G, et al. Development of polyneuropathy during thalidomide therapy. Br J Dermatol 1985; 112: 475–80

    Article  PubMed  CAS  Google Scholar 

  61. Gutierrez-Rodriguez O, Starusta-Bacal P, Gutierrez-Montes O. Treatment of refractory rheumatoid arthritis — the thalidomide experience. J Rheumatol 1989; 16: 158–63

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schuler, U., Ehninger, G. Thalidomide: Rationale for Renewed Use in Immunological Disorders. Drug-Safety 12, 364–369 (1995). https://doi.org/10.2165/00002018-199512060-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-199512060-00002

Keywords

Navigation