Thalidomide suppresses T- and B-cell responses to myelin antigen in experimental allergic neuritis.
The effects of thalidomide and, for reference, dexamethasone on T- and B-cell functions were assayed in vitro in Lewis rats with experimental allergic neuritis induced by active immunization with bovine peripheral nerve myelin (BPM) and complete Freund's adjuvant. Thalidomide and dexamethasone at the concentration ranges 10(-5)-10(-7) g/ml and 4 x 10(-5)-4 x 10(-9) g/ml, respectively, both inhibited phytohemagglutinin (PHA)- and BPM-induced T-cell proliferation as well as levels of PHA- and BPM-reactive interferon (IFN)-gamma-secreting cells, reflecting the suppression of Th1-like cells. The effect of dexamethasone was most pronounced on PHA-induced T-cell proliferation and IFN-gamma secretion, whereas the effect of thalidomide was most pronounced on BPM-induced T-cell proliferation and IFN-gamma secretion. Thalidomide reduced the B-cell responses to both BPM and Mycobacterium tuberculosis purified protein derivative, but to a lesser extent than dexamethasone. The in vitro design described could be useful to evaluate compounds with putative immunomodulatory activities. The inhibitory effects of thalidomide on autoantigen-induced Th1-cell functions may warrant the use of this substance in T-cell-mediated autoimmune diseases.
Zhu
J
J
Division of Neurology, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden.
Bai
X
X
Mix
E
E
van der Meide
P H
PH
Zwingenberger
K
K
Link
H
H
D000818:Animals; D001324:Autoantigens; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology; D007074:Immunoglobulin G / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D018996:Myelin P2 Protein; D009444:Neuritis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013792:Thalidomide / Q000494:pharmacology*
D001324:Autoantigens; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018996:Myelin P2 Protein; D013792:Thalidomide; D003907:Dexamethasone; D007371:Interferon-gamma