MACROPHAGE-DERIVED NITRIC-OXIDE IS INVOLVED IN THE DEPRESSED CONCANAVALIN-A RESPONSIVENESS OF SPLENIC LYMPHOCYTES FROM RATS ADMINISTERED MORPHINE IN-VIVO

The present study examined the role of macrophage-derived nitric oxide in the suppressive effect of in vivo morphine administration on Con A -stimulated proliferation of splenic lymphocytes in rats. The results showed that concentrations of nitrite are significantly greater in Con A-stimulated splenocyte cultures from morphine-treated rats than in c ultures from saline-treated rats, and that the depletion of macrophage s from splenocyte cultures abolishes the suppressive effect of morphin e on Con A-stimulated proliferation. Moreover, the addition of N-G-mon omethyl-L-arginine (NMMA) to Con A-stimulated splenocyte cultures atte nuates the suppressive effect of morphine on mitogenic responsiveness. The addition of excess L-arginine to splenocyte cultures containing N MMA reverses the effect of NMMA and restores morphine's suppressive ef fect on Con A-stimulated proliferation, but the addition of D-arginine to splenocyte cultures containing NMMA does not restore the suppressi ve effect of morphine. Taken together, these findings demonstrate that the suppressive effect of in vivo morphine administration on Con A-st imulated proliferation of splenic lymphocytes involves macrophage-deri ved nitric oxide.