RESUMEN
Met-enkephalin (MENK) increased superoxide anion release by human polymorphonuclear cells (PMNs) at a physiological (10(-10) M) concentration and decreased release at a relatively high (10(-8) M) concentration. Surprisingly, naloxone (NAL), used as a specific antagonist in these experiments, displayed immunomodulatory actions of its own, increasing superoxide anion release at 10(-10) and 10(-8) M concentrations. Although both were effective, the dose-response curves were different for NAL and MENK. NAL and MENK also had a combined influence on O2- release. The stimulative effect of 10(-10) M MENK could be abolished by 10(-8) M NAL in seven of eight cases. Unexpectedly, the stimulatory effect of 10(-8) and 10(-10) M NAL could be abrogated by MENK in five of eight cases as well. The fact that NAL and MENK mutually interfere with one another in their effect upon O2- release by human PMNs discredits NAL as an appropriate antagonist in this system.
Asunto(s)
Encefalina Metionina/antagonistas & inhibidores , Naloxona/farmacología , Neutrófilos/efectos de los fármacos , Superóxidos/metabolismo , Adulto , Depresión Química , Encefalina Metionina/farmacología , Humanos , Neutrófilos/metabolismoRESUMEN
The effect of Met-enkephalin (MENK) on several immune functions, corticosterone (CS) and adrenocorticotropin (ACTH) levels in the plasma was studied in adrenalectomized (ADX) and sham-adrenalectomized (SADX) mice. Multiple Met-enkephalin injections (10 mg/kg per day in two injections 12 h apart, for 4 days) increased the plaque-forming cell response to sheep erythrocytes in the spleen and enhanced the proliferation of spleen cells in vitro. These effects were comparable in sham-adrenalectomized and adrenalectomized mice. However, spleen cells of mice immunized with sheep red blood cells and injected with Met-enkephalin, showed suppressed blastogeneic transformation with Con A. The effect was equal in adrenalectomized and sham-adrenalectomized mice. In the absence of Con A in spleen cell cultures, MENK treatment of donor mice resulted in a significant mitogenic effect. NK activity of the spleen cells was suppressed in MENK-treated adrenalectomized mice. Injection of MENK decreased corticosterone levels and increased ACTH levels in the plasma of sham-adrenalectomized mice. In adrenalectomized mice plasma levels of ACTH were decreased by MENK. It seems that corticosteroid secretion, although changed by adrenalectomy and influenced by treatment with MENK, does not influence the modulatory effect of MENK on the PFC response and blastogeneic transformation of mouse spleen cells. However, NK activity of the spleen cells treated with MENK seems to the reflect joint action of MENK and corticosteroids.