AUGMENTING EFFECT OF OPIOID-PEPTIDES ON MURINE MACROPHAGE ACTIVATION

We investigated the effect of several opioid peptides on the activatio n of murine peritoneal exudate macrophages (M phi) in vitro. M phi wer e treated with interferon (IFN) as a priming agent and bacterial lipop olysaccharide (LPS) as a triggering agent in the presence or absence o f opioid peptides. M phi activation was assessed by their tumoricidal activity. When treatment with IFN and LPS resulted in a high level act ivation of M phi, dynorphin-A exerted no further enhancing effect. Whe n treatment induced only weak activation, however, dynorphin-A augment ed the M phi activation. Leucine-enkephalin, methionine-enkephalin, an d also beta-endorphin had augmenting effects. An opioid receptor antag onist, naloxone, reduced the effect of dynorphin-A and beta-endorphin. When M phi were treated sequentially with IFN and LPS, beta-endorphin operated in combination with LPS only. Moreover, beta-endorphin was e ffective for already activated M phi. These results indicate that opio id peptides act on M phi via classical opioid receptors, and that resp onsiveness to opioid peptides is induced in the triggering stage of M phi activation.