Gastrointestinal regulatory peptides modulate mouse lymphocyte functions under serum-free conditions in vitro.
Conditions are described for performing mitogen (Concanavalin A, Con A; lipopolysaccharide, LPS) and mixed lymphocyte reaction (MLR) cultures using serum-free medium. The effects of exogenously adding several gastrointestinal regulatory peptides (beta-endorphin, substance P, met-enkephalin, vasoactive intestinal peptide, bombesin and somatostatin) on the incorporation of 3H-methyl-thymidine was determined. It was observed that mitogen stimulation of lymph node cells with Con A was inhibited (70% of control) by vasoactive intestinal peptide (VIP) but spleen cells stimulated by LPS were insensitive to immunomodulation (98% of control). The ability of VIP to inhibit Con A induced thymidine incorporation was concentration dependent (10(-6) to 10(-18) M) and was not attributable to kinetic shifts or cell toxicity. None of the other tested neuropeptides affected Con A or LPS induced blastogenesis. MLR cultures were inhibited by VIP, beta-endorphin and somatostatin in a biphasic manner with maximal inhibition observed at 10(-8) to 10(-12) M. Both substance P and bombesin exhibited slight immunoenhancing properties at 10(-14) to 10(-18) M. Met-enkephalin was ineffective as an immunomodulator of MLR cultures. The utility of using serum-free medium in identifying neuropeptides with immunomodulatory properties are discussed.
D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D004064:Digestive System / Q000187:drug effects*; D004723:Endorphins / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D013004:Somatostatin / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D001615:beta-Endorphin
D004723:Endorphins; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D003208:Concanavalin A; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D004744:Enkephalin, Methionine; D001615:beta-Endorphin; D001839:Bombesin