Effect of ergot-alkaloid dihydroergosine on the immune reaction and plasma corticosterone in rats.

Ergot-alkaloid dihydroergosine, a potential antidepressive and anxiolytic drug, suppressed humoral and cellular immune reaction in rats, if given in a single injection (2-100 mg/kg) 1 hour after immunization. Plasma corticosterone levels were decreased upon assay of the immune response, 5 or 8 days following treatment.

Met-enkephalin modulates stress-induced alterations of the immune response in mice.

Overnight restraint stress of mice decreased ConA-driven lymphocyte proliferation, plaque-forming cell response to sheep red blood cells (SRBC), and NK activity in the spleen, but the phagocytic activity was enhanced. Injection of methionine-enkephalin (MENK), 10 mg/kg, i.p., 30 min before restraint, abolished these changes (except for the NK activity) and attenuated the stress-induced elevation of glucocorticoids. However, MENK itself affected the immune responses like stress: It decreased NK activity and the PFC response and enhanced phagocytic activity. Contrary to results with stress, MENK had no effect on cell proliferation. The opioid-receptor antagonist naloxone given before restraint reversed the stress-induced enhancement of phagocytosis and the decrease of T-cell proliferation. Alterations of the immune responses induced by restraint stress seem to be mediated by at least two mechanisms: activation of the hypothalamus-pituitary-adrenal (HPA) axis and the secretion of opioid peptides. MENK injected before stress may interfere with either or both mechanisms. T or B lymphocytes seem to be affected by the activation of the HPA axis, and phagocytes by a direct opioid action, whereas NK cells seem to be under the influence of another control mechanism.

Serotonin, serotoninergic agents and their antagonists suppress humoral immune reaction in vitro.

Serotonin (5-HT), its derivative 5-methoxy-tryptamine (MeOT) and ergot-alkaloid dihydroergosine (DHESN) suppressed the immune reaction of mouse spleen cells against sheep erythrocytes in vitro (PFC assay). Ketanserin and propranolol, antagonists of 5-HT, also caused suppression. However, cells incubated with propranolol 20 min before 5-HT or MeOT produced as many plaques as the non-treated cells. Preincubation with ketanserin resulted in similar interference, but the reversal was not complete. It is concluded that serotonin and related agents probably affect several types of immunocompetent cells participating in successive stages of the PFC reaction. The antagonists probably interfered via 5-HT receptors, adrenergic receptors or both. Immunosuppression observed with serotoninergic agents and their antagonists draws attention to possible side effects of such drugs.

Serotonin and serotoninergic agents affect proliferation of normal and transformed lymphoid cells.

Blastogenic transformation of murine spleen cells elicited with concanavalin A was suppressed by serotonin 10(-12) to 10(-6) M, and marginally stimulated by its antagonists ketanserin and propranolol in low concentrations (10(-15) to 10(-11) M). Ketanserin (5-HT2 receptor ligand) and propranolol (5-HT1A and beta-adrenergic ligand) did not block the suppressive effect of serotonin if used along with it in equimolar concentrations (10(-9) M). Ergot-alkaloid dihydroergosine suppressed, whereas dihydroergotoxin stimulated the blastogenic transformation. Opposite effects of the agents were obtained in experiments with mouse myeloma X63/Ag 8.653 and hybridoma SHV 125 cell lines, which unlike normal lymphoid cells, are homologous cell populations and proliferate spontaneously. The data indicate that serotonin and its antagonists interfere directly with mitosis and/or autocrine stimulation of target cells.