The effect of somatostatin on the production of human interferons by mononuclear cells

Somatostatin (SMS) is a tetradecapeptide which can inhibit the secretion of a number of peptides produced by the endocrine or nervous systems. SMS 201-995 (octreotide) is a somatostatin analogue with very potent somatostatin activities. We have been investigating the effects of both SMS and octreotide on the production of human interferon (IFN). We obtained human peripheral blood mononuclear cells from normal donors and induced them to produce IFN in the presence or absence of a number of peptides possessing somatostatin activities. SMS and octreotide were shown to inhibit the secretion of INF-gamma but not IFN-alpha. Concentrations of 10(-6) M were shown to decrease yields when Concanavalin A or phytohemagglutin were used as the inducer. Higher concentrations had a progressively greater effect. No effects were observed on IFN-gamma production if interleukin 2, ionomycin, or various natural antigens were used to induce the cells. The 28-amino acid form of somatostatin had some effects on gamma IFN yields but the first 14-amino acid fragment of this peptide moiety did not. No effect of any of these compounds was observed on IFN bioactivity. These studies indicate SMS may have some regulatory action on the secretion of immunomodulators in vitro but the concentrations required are well above those encountered under physiologic circumstances, suggesting SMS may not play an important regulatory role governing such secretion in vivo.