Gender-related differences in murine T- and B-lymphocyte proliferative ability in response to in vivo [Met(5)]enkephalin administration

Gender-related differences in response to drugs of abuse, such as cocaine a nd morphine, have been reported both in humans and in experimental animals. Besides causing analgesia, morphine has recently been shown to exert stron g immunosuppressive activity. However, no data on the influence of gender o n the immunomodulatory effects of morphine or opioid peptides have been rep orted yet. The aim of this study was to test the influence of gender on the immunomodulatory ability of the endogenous opioid peptide [Met(5)]enkephal in (MENK) in mice. This was done by comparing the proliferative ability of splenic T- and B-lymphocytes 14 h after systemic (intraperitoneal; i.p.) ad ministration of [Met(5)]enkephalin (2.5, 5 or 10 mg/kg body weight). The pr oliferative ability of T- and B-lymphocytes was assessed by testing their i n vitro response to graded concentrations of the T- and B-cell mitogens, co ncanavalin-A (Con-A) and lipopolysaccharide (LPS), respectively. The result s obtained showed that [Met5]enkephalin, at a dose of 2.5 mg/kg, enhanced t he proliferative ability of T-lymphocytes in male mice, but not in female m ice. Similarly, [Met(5)]enkephalin, at doses of 2.5 and 5 mg/kg, enhanced t he proliferative ability of splenic B-lymphocytes in male mice, whereas in female mice a decrease was observed ([Met(5)]enkephalin 2.5 mg/kg, LPS 10 m u g/ml). [Met(5)]enkephalin, at a dose of 10 mg/kg, did not affect the prol iferative ability of either lymphocyte population, regardless of gender. Th e [Met(5)]enkephalin-induced stimulatory effect on both T- and B-lymphocyte proliferation was reversed by naloxone (10 mg/kg body weight), injected pr ior to [Met(5)]enkephalin, suggesting an involvement of opioid receptors. T hus, the data presented provide evidence for the gender-related response of murine splenic lymphocytes to immunomodulation by [Met(5)]enkephalin, admi nistered in vivo. This finding may be relevant to the potential use of [Met (5)]enkephalin in adjuvant therapy for immunocompromised states, such as ac quired immunodeficiency syndrome (AIDS) or malignancies. (C) 2000 Published by Elsevier Science B.V. All rights reserved.