Involvement of cyclic amp in the regulation of lymphokine induced glia cell stimulation

Abstract T and B lymphocytes of human or murine origin were found to secrete a factor which increases the DNA and RNA synthesis of cultured glia cells. This factor, termed glia cell stimulating factor (GSF), is released upon stimulation of such immune cells by mitogen or antigen qualifying it as a lymphokine. In this communication we report on the role of cyclic AMP (cAMP) in regulating the effect of GSF on glia cells. Prostaglandin E 1 (PGE 1 ), isoproterenol and theophylline were effective in suppressing the GSF-induced increase of the glia cell proliferation. No inhibition of DNA synthesis and no decrease in cell number was observed when testing these substances on glia cells not being activated by GSF. The drugs were found to induce an increase in cAMP concentrations of glia cells. A partial desensitization of the glia cells to these drug induced elevations of cAMP was detected after pretreatment of the glia cell cultures with GSF. It is suggested that stimulated lymphocytes not only release GSF but also low molecular weight proteins such as PGE 1 which regulate the effects of GSF on glia cells by activating their adenylate cyclase.