Effect of cyclosporine on host defence.

To discover whether cyclosporine administered daily in therapeutic equivalent doses for 3 consecutive weeks suppressed host defence, the authors measured the delayed-type hypersensitivity (DTH) skin response to keyhole-limpet hemocyanin (KLH) in rats. Twenty, male, Sprague-Dawley rats were sensitized to KLH and reactivity was confirmed 14 days later. Following sensitization, cyclosporine (20 mg/kg orally) was administered daily for 21 days to 10 rats. The other 10 (control group) received equivalent volumes of diluent (polysorbate 80 and ethanol). There was no difference in the DTH response between the cyclosporine and control groups for 5 weeks following treatment. Larger doses of cyclosporine (100 mg/kg) given intraperitoneally 30 minutes before and 6 hours after skin testing, suppressed the DTH response (7.2 mm to 2.4 mm) but resulted in a high mortality (eight of nine rats) at 48 hours. Delayed-type hypersensitivity was also suppressed in the control group but to a lesser extent and with no deaths (6.4 to 3.9 mm, p less than 0.05). Cyclosporine, in therapeutic equivalent doses, does not suppress the nonspecific immune component of host defence as reflected by the DTH skin response in previously sensitized animals. This may partially explain the lower frequency of septic morbidity and mortality in cyclosporine-treated transplant patients, compared with those receiving conventional therapy.