IMMUNOSUPPRESSIVE EFFECTS OF HYPERICIN ON STIMULATED HUMAN-LEUKOCYTES- INHIBITION OF THE ARACHIDONIC-ACID RELEASE, LEUKOTRIENE B-4 AND INTERLEUKIN-1-ALPHA PRODUCTION, AND ACTIVATION OF NITRIC-OXIDE FORMATION

The present study describes the influence of hypericin of Hypericum pe rforatam on TPA- and LPS-induced arachidonic acid (AA) metabolism, as well as interleukin 1 alpha and nitric oxide (NO) production in human immunocompetent cells. The results show that hypericin inhibits the re lease of arachidonic acid (AA) from membrane phospholipids in calcium ionphore A23187-TPA stimulated human granulocytes in a dose-dependent manner (IC50, 4 mu M), but that calcium ionophore is not the only indu cer. An inhibitory effect could be observed at concentrations of < 0.4 mu M and in the presence of low concentrations of TPA (0.16 - 0.32 mu M). As a result of this inhibition hypericin inhibits the release of LTB(4) but not of PGE(2). Hypericin also inhibits the production of IL -1 alpha in LPS-stimulated human monocytes and activates NO production in isolated human leukocytes. This effect is comparable to the effect of LPS and is probably not associated with the IL 1 alpha or intermed iates of the cycloxygenase pathway. The results as a whole let us assu me that one important mechanism for the antiviral, antiinflammatory an d antitumoral effects of hypericin and Hypericum extracts is the inhib ition of the PKC-mediated signalling pathway which in turn influences the AA metabolism, and the interleukin-1 alpha production resulting in an immunosuppressive effect on the host immune system.