Effects of formalin-induced pain on ACTH, beta-endorphin, corticosterone and interleukin-6 plasma levels in rats.

The behavioral and immunoendocrine effects of formalin-induced pain were studied in male rats following a subcutaneous injection of formalin (50 microliters; 0.1%, F01 groups, 10%, F10 groups) or sham injection (control groups). After treatment, animals were tested in a transparent open field for either 30 or 60 min and thereafter sacrificed by decapitation. Plasma was collected for adrenocorticotropic hormone (ACTH), corticosterone, beta-endorphin (beta-EP) and interleukin-6 (IL-6) determinations. Pain-evoked responses (licking, flexing, paw jerk), standard measures of activity (locomotion, rearing, olfactory exploration) and self-grooming were recorded. The higher formalin concentration induced stronger pain-evoked behavioral responses, paralleled by higher levels of ACTH, beta-EP and IL-6, but did not affect the other behavioral parameters. In contrast, the lower formalin concentration induced a marked increase in locomotion and rearing and a decrease in ACTH levels. In both formalin-injected groups, corticosterone did not differ from controls.

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.

[In vitro effects of peptides of the corticostatin/defensin family on production of mitogen-induced cytokines]. / Effetti in vitro di peptidi della famiglia delle corticostatine/defensine sulla produzione di citochine indotta da mitogeni.

Cytokines are autocrine, paracrine and endocrine glycoproteins that interact with specific cell receptors and have pleiotropic effects. Increasing evidence indicates that cytokines, immune interferon (IFN-gamma) and interleukin 6 (IL-6) among others, modulate hypothalamic-pituitary-adrenal function. Corticostatins/defensins are a family of cationic peptides recently isolated from phagocytic cells of myeloid lineage. Four peptides have been isolated from human neutrophils: HP-1, 2, 3 and 4. As defensins they participate in immunosurveillance against viruses, bacteria and fungi. Some members of the family are also able to inhibit ACTH-induced steroidogenesis. Among human peptides, only HP-4 is corticostatic. We previously demonstrated that HP-1 and HP-4 inhibit in vitro the spontaneous and cytokine-inducible natural killer activity of human peripheral blood mononuclear cells (PBMC) and potentiate cortisol-dependent inhibition. The present work was carried out to determine whether two human corticostatins/defensins, HP-1 and HP-4, were able to modulate in vitro IFN-gamma and IL-6 production by human PBMC stimulated with phytohemagglutinin or Concanavalin A. IFN-gamma was titrated using biological assay with WISH cells as indicators and vesicular stomatitis virus as the challenge virus. IL-6 was measured by means of enzyme amplified sensitivity immunoassay. Both HP-1 and HP-4 significantly reduced cytokine production. Our data indicate that HP-1 and HP-4 are novel modulators of lymphocyte functions in vitro. Their depressing properties on ACTH-induced steroidogenesis and on cytokine production add complexity to neuroendocrine-immune circuits involving hypothalamic-pituitary-adrenal function.