LYMPHOKINES PRODUCTION BY CONCANAVALIN A-STIMULATED MOUSE SPLENOCYTES- MODULATION BY MET-ENKEPHALIN AND A RELATED PEPTIDE

Methionine-enkephalin (ME) and its synthetic congener Tyr-D-Ala-Gly-Me -Phe-Gly-NH.C3H7-iso (82/205), in a concentration-dependent biphasic m anner modulated the concanavalin A (Con A)-stimulated phagocytosis-pro moting (PP)-activity elaboration in the culture supernatants of mouse splenocytes in vitro. Bath these peptides at 1 x 10(-5) and 1 x 10(-6) M inhibited the production of PP activity; conversely, at 1 x 10(-7)- 1 X 10(-9) M they augmented it. Peptide 82/205 was nearly 1.2-fold mor e inhibitory and approximately 1.8-fold more potent in augmenting the PP activity elaboration. The PP activity appeared to be due to lymphok ines (LK) gamma interferon and interleukin-4 as the neutralizing conce ntrations of monoclonal antibodies against these LK significantly (p<0 .05) inhibited it. Cycloheximide (50.0 mu g/ mi) completely inhibited the production of LK indicating their de novo synthesis. The peptides appeared to exert their inhibitory and augmenting effects via delta-an d mu-opioid receptors, respectively, as pretreatment of splenocytes wi th 100-fold higher (1 x 10(-3) M) concentration of naloxone was requir ed to block their inhibitory effect; the augmenting effect was blocked by 1 x 10(-5) M only. None of the peptides or naloxone could directly stimulate the splenocytes for PP-LK elaboration.