Alleviation of cyclosporin-induced immune suppression by the cytokine inducer ADA-202-718.
ADA-202-718 (ADA) has been shown to augment the production of various cytokines (IL-1, IL-2 and gamma-interferon) by murine T lymphocytes. Administration of 1 mg/kg/day to mice from the time of immunization significantly enhanced delayed-type hypersensitivity responses to sheep red blood cells (SRBC). ADA also inhibited immune suppression in mice given 25 but not 50 mg/kg/day cyclosporin A (CsA). There were, however, few changes compared with vehicle-treated controls in the numbers of splenic regulatory T cell subsets (L3T4+ and Ly2+) following treatment with CsA, ADA or both drugs. On the other hand, splenic lymphocytes from ADA-treated animals exhibited augmented proliferative responses to polyclonal T and B cell mitogens and antigen. ADA (1 mg/kg) also stimulated the splenic IgM plaque-forming cell response to SRBC and prevented CsA (25 mg/kg)-induced suppression of humoral immunity. In vitro, ADA (2 micrograms/ml) inhibited CsA-induced suppression of T cell proliferation, the effect being most marked at lower inhibitory concentrations of CsA. These data illustrate the capacity of ADA to augment or restore T cell responses in experimental animals and are consistent with the view that CsA acts in these experimental in vivo systems by inhibition of cytokine production.
Woo
J
J
Department of Pathology, University of Aberdeen, Foresterhill, Scotland, U.K.
Thomson
A W
AW
D000818:Animals; D000917:Antibody Formation; D001685:Biological Factors / Q000378:metabolism*; D003524:Cyclosporins / Q000494:pharmacology*; D016207:Cytokines; D004220:Disulfides / Q000494:pharmacology*; D004342:Drug Hypersensitivity; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006968:Hypersensitivity, Delayed / Q000139:chemically induced; D007165:Immunosuppression Therapy; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D013154:Spleen / Q000166:cytology
D001685:Biological Factors; D003524:Cyclosporins; D016207:Cytokines; D004220:Disulfides; C045470:ethylene-2,2'-bis(dithio)bis(ethanol)