RESUMO
OBJECTIVES: The aim of this research consisted in studying the effects of tetrapeptide Epitalon on both thymocyte proliferation and interleukin-1beta (IL-1beta) signal transduction via sphingomyelin pathway in the cerebral cortex membranes of mice exposed to stresses exerting diverse effects upon humoral immune response. DESIGN AND SETTING: The experiments were performed on male (CBAxC(57)BL(6))F1 mice aged 8 10 weeks. Two models of experimental stress were used: immune-stimulatory rotation stress and immune-suppressive combined stress (cooling followed by immobilization). The concomitant effect of Epitalon was determined according to its influence on thymocyte proliferation stimulated by concanavalin A at a sub-optimal dose and recombinant IL-1beta. The activity of membrane neutral sphingomyelinase (nSMase), the key enzyme of the sphingomyelin signal transduction pathway, was assayed according to modified Rao and Spence's method (1976). RESULTS: The investigation demonstrated that Epitalon increased thymocyte proliferative activity, both enhanced under rotation stress and suppressed under combined one. It also increased IL-1beta concomitant effect. These findings corresponded to Epitalon effect on diverse stress-induced changes in nSMase activity in cerebral cortex fraction P2. Epitalon activated nSMase in the cerebral cortex membranes of intact mice and increased IL-1beta stimulatory effect on the enzyme activity. CONCLUSIONS: The obtained results provided a conclusive evidence of Epitalon stress-protective effect at the level of IL-1beta signal transduction via sphingomyelin pathway in the nerve tissue, as well as at the level of target thymocyte proliferation.