THE ROLE OF CYTOKINES IN MET-ENKEPHALIN-MODULATED NITRIC-OXIDE RELEASE

In the present study the in vitro and in vivo effect of Met-enkephalin (MENK) on nitric oxide (NO) release by mouse peritoneal macrophages w as evaluated. While in vitro MENK was ineffective unless combined with suboptimal concentrations of recombinant murine interferon gamma, in vive all the doses (2.5, 5 or 10 mg/kg bw) bimodaly modulated NO relea se. Only the stimulative (2.5 and 10 mg/kg bw) and not the suppressive (5 mg/kg bw) dose of MENK was opioid receptor-mediated as demonstrate d by abolishing the effect by naloxone. The stimulative effect of the low (2.5 mg/kg bw) dose, that was observed only if MENK was injected p .m., was associated with the IL production and IFN gamma as demonstrat ed by abolishing the effect by specific antibodies. The data additiona lly support the idea that opioid-mediated responses might be to a larg e degree mediated by the release of cytokines.