Corticostatins/defensins inhibit in vitro NK activity and cytokine production by human peripheral blood mononuclear cells.

Corticostatins/defensins are a family of cationic peptides recently isolated from phagocytotic cells of the myeloid lineage. Natural killer (NK) cells are spontaneously cytotoxic large granular lymphocytes that are involved in immunosurveillance against cancer and infections. Their activity is modulated by hormones of the hypothalamic-pituitary-adrenal axis. We wished to determine whether two human corticostatins/defensins, HP-1 and HP-4, are able to change in vitro the spontaneous NK activity of human peripheral blood mononuclear cells (PBMC) and the responses either to the stimulatory cytokines immune interferon (IFN-gamma) or interleukin 2 (IL-2) and to the inhibitory hormone cortisol. NK cell activity was measured in a 4-h direct cytotoxicity assay with K562 cells as a target. HP-1 and HP-4 (10 (-8) -10 (-9) M) significantly inhibited the spontaneous and cytokine-inducible NK activity, and increased the cortisol-dependent inhibition. Radioimmunoassay of HPLC purified fractions obtained from sonicated NK cells showed HP-1 in the two cell preparations examined. We also evaluated the effects of HP-1 and HP-4 (10 (-8) M -10(-9) M) upo IFN-gamma and interleukin 6 (IL-6) production by PBMC stimulated with phytohemagglutinin (PHA) or concanavalin A (ConA). IFN-gamma was titrated with the biological assay using WISH cells as indicators and vescicular stomatitis virus (VSV) as the challenge virus. IL-6 was measured using an enzyme amplified sensitivity immunoassay. Both HP-1 and HP-4 significantly reduced cytokine production. Our data indicate that corticostatins/defensins are novel modulators of lymphocyte functions in vitro. Their immunodepressing properties could add complexity and plasticity to hypothalamic-pituitary-adrenal-cytokine circuits in vivo.

Immune and endocrine aspects of social and territorial behavior in male rabbits.

Although there have been some studies of the relation between behavior and mitogen-induced lymphocyte proliferation and immunoglobulin synthesis, few data are available about the effect of behavior on specific lymphokine production. In this study, we describe the effect of social and territorial behaviors on interferon-gamma (IFN-gamma) production by concanavalin A-stimulated peripheral blood mononuclear cells (PBMCs) in pairs of socially naive male rabbits living in a seminatural open-air environment. We also assayed PBMC glucocorticoid receptors (GcRs) and plasma corticosterone (C). Three groups of behaviors were identified: agonistic (Mount and Follow), affiliative (Groom) and territorial (Mark and Dig). Mount was correlated with Follow, while Mark was correlated with Dig. Groom was correlated with all the other behaviors. Groom, Mark, Mount and Follow were all positively correlated with PBMC GcRs. Groom and PBMC GcRs were each negatively correlated with plasma C. The two rabbits in each pair could be distinguished in terms of territorial behavior, since one animal always had a higher score. The animals with the higher level of territorial behavior within the pairs exhibited a significant increase in IFN-gamma production at the end of the experimental period. They also showed a positive correlation between the percentage variations of IFN-gamma production and PBMC GcRs. It is suggested that social factors, especially territorial behavior, affect adrenocortical activity and IFN-gamma production.

Immune and neuroendocrine response to restraint in male and female rats.

A parallel study of the modification in the opioid and immunological systems induced by acute restraint (RT) was carried out in male and female rats 24 hr after the treatment. beta-Endorphin-like immunoreactivity (beta-ELI) was measured in two brain areas (ventral hypothalamus [HYP] and periaqueductal gray matter [PAG]) and in the pituitary (anterior and neurointermediate lobes), together with plasma corticosterone (C) and ACTH. Immune function was measured as mitogen-induced Interferon-gamma (IFN-gamma) production by splenocytes. RT reduced beta-ELI levels in the PAG in males and females. Plasma levels of C and ACTH did not differ from the basal levels in restrained animals. RT reduced IFN-gamma production in both sexes, but this effect was more marked in females than in males. The possible relationship between the immune and opioid system is discussed.