Reversal by lymphokines of the effect of cyclosporin A on contact sensitivity and antibody production in mice.
Cyclosporin A (CsA) treatment of mice during the first 4 days of the sensitization phase prevents induction of contact sensitivity to trinitrochlorobenzene (TNCB). Administration of CsA on the day of ear challenge with TNCB also inhibits the effector phase of this response. Simultaneous treatment of the mice with IL 2-containing murine lymphokine preparations or with recombinant human IL 2 reverses the effect of CsA on the induction of contact sensitivity. Recombinant IL 2 also reverses the inhibition by CsA of the effector phase. Neither phase of the response is restored by murine IFN-gamma. Anti-body production to trinitrophenylated (TNP) Ficoll or TNP-hemocyanin is also strongly inhibited (greater than 75%) by CsA injected on the day of antigen injection. Although lymphokines or endotoxin may strongly enhance these responses, no reversal of the effect of CsA can be obtained. We conclude that inhibition of IL 2 production is of paramount importance for the inhibitory effect of CsA on contact sensitivity, but that additional effects are involved in the inhibition of antibody production to both T-dependent and T-independent antigens.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D003524:Cyclosporins / Q000494:pharmacology*; D003877:Dermatitis, Contact / Q000209:etiology / Q000276:immunology*; D005260:Female; D005362:Ficoll / Q000031:analogs & derivatives / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D006462:Hemolytic Plaque Technique; D007376:Interleukin-2 / Q000502:physiology; D008222:Lymphokines / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000502:physiology; D014301:Trinitrobenzenes / Q000276:immunology
D003524:Cyclosporins; D007376:Interleukin-2; D008222:Lymphokines; D011994:Recombinant Proteins; C020529:TNP-ficoll; D014301:Trinitrobenzenes; D005362:Ficoll; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin