Lymphokines production by concanavalin A-stimulated mouse splenocytes: modulation by Met-enkephalin and a related...

Methionine-enkephalin (ME) and its synthetic congener Tyr-D-Ala-Gly-Me-Phe-Gly-NH.C3H7-iso (82/205), in a concentration-dependent biphasic manner modulated the concanavalin A (Con A)-stimulated phagocytosis-promoting (PP)-activity elaboration in the culture supernatants of mouse splenocytes in vitro. Both 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 more inhibitory and approximately 1.8-fold more potent in augmenting the PP activity elaboration. The PP activity appeared to be due to lymphokines (LK) gamma interferon and interleukin-4 as the neutralizing concentrations of monoclonal antibodies against these LK significantly (p < 0.05) inhibited it. Cycloheximide (50.0 micrograms/ml) completely inhibited the production of LK indicating their de novo synthesis. The peptides appeared to exert their inhibitory and augmenting effects via delta- and mu-opioid receptors, respectively, as pretreatment of splenocytes with 100-fold higher (1 x 10(-3) M) concentration of naloxone was required 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.