Characteristics of cyclosporine induction of increased prostaglandin levels from human peripheral blood monocytes

Human monocytes (M phi) exposed to 0.5-20 micrograms/ml of cyclosporine (CsA) produced levels of prostaglandins of the E series (PGE) that were 2-3-fold greater than control M phi cultured in medium alone. Maximal PGE levels were obtained at 24-48 hr incubation, and the failure to observe a linear increase of PGE levels at higher CsA concentrations appeared partially related to cytotoxic effects. CsA was considerably less effective than phorbol myristate acetate or bacterial lipopolysaccharide in increasing PGE production, but the PGE levels achieved with CsA approximated those known to suppress immune responsiveness. Other experiments showed that, although the increased PGE production with CsA was indomethacin-sensitive, CsA mostly functioned to increase the availability of free arachidonic acid (AA) instead of accelerating AA conversion by the cyclooxygenase pathway. Thus CsA can alter M phi physiology, and these alterations might inhibit quite early events during the induction phase of immune responses.