SUPPRESSION OF DELAYED-TYPE HYPERSENSITIVITY REACTIONS AND LYMPHOKINE PRODUCTION BY CYCLOSPORIN-A IN THE MOUSE

  • 1 January 1983
    • journal article
    • research article
    • Vol. 52  (3) , 599-606
Abstract
Two consecutive daily i.m. injections of cyclosporin A (Cs A) (> 50 mg/kg) inhibited delayed type hypersensitivity (DTH) responses in mice immunized with SRBC [sheep red blood cells]. Maximal suppression was observed when Cs A was administered 24 and 48 h after sensitization. Culture of spleen cells from these animals with antigen, insoluble concanavalin A (iCon A) or PHA [phytohemagglutinin] revealed inhibition of the production of 2 lymphokines: that inducing macrophage procoagulant activity (MPCA) and macrophage chemotactic factor (LDCF). The inhibitory effect on lymphokine production was not due to depletion of T cells. In vitro, 25 ng/ml Cs A suppressed T cell proliferative repsonses to antigen and mitogen but much higher doses were required to impair the response to LPS [Escherichia coli lipopolysaccharide]. Similar doses of Cs A also suppressed lymphokine production, but the responses of macrophages to these lymphokines was unaffected, even at doses which totally inhibited lymphokine production. Production of interleukin 1 by LPS stimulated macrophages was inhibited by Cs A only at concentrations much greater than those required to suppress lymphokine production.