Modulation of delayed-type hypersensitivity reactions by cyclosporin A
The investigations have given rise to the following findings: 1. CsA is an effective immunosuppressant of both the induction and elicitation phases of tuberculin-like and contact delayed-type hypersensitivity (DTH) and of the induction phase of Jones-Mote hypersensitivity. 2. The effective suppression of tuberculin-like DTH responses in the guinea pig is not dependent upon cyclophosphamide-sensitive suppressor cells. 3. Topically applied CsA inhibits the elicitation of contact dermatitis in experimental animals. 4. The kinetics of percutaneous CsA absorption have been determined, as has the extent to which this mode of drug delivery obviates systemic toxicity. 5. The investigation of CsA-induced DTH enhancement indicates that the phenomenon is restricted to cellular as opposed to humoral responses, develops some days after drug withdrawal and can be reversed by the administration of putative suppressor cells from immunised but untreated animals. 6. CsA is able to effectively inhibit T cell dependent hyper-eosinophilia. It would appear that the effects of CsA on DTH responses and on T dependent eosinophilia occur primarily by the inhibition of T helper cell function. Enhancement phenomena seem to arise from drug impaired development of antigen-specific suppressor cells which, following drug withdrawal, fail to develop, in contrast to the maturation of T effector cells. Although the phenomenon of enhancement may limit the potential of CsA in the control of diseases in which DTH responses are a component, topical application is effective and may well be suitable for use over a prolonged period without systemic toxicity.