Capsaicin attenuates immunosuppression induced by chronic stress in BALB/C mice.

Although acute stress generally exerts positive effects on the immune system, chronic stress typically causes immunosuppression via the hypothalamic-pituitary-adrenal (HPA) axis. In this study, the effects of capsaicin (1.28 mg/kg intraperitoneally [i.p.] for 7 days) on immune parameters were evaluated under conditions of chronic stress. Capsaicin treatment significantly increased the immune response as evaluated by the delayed-type hypersensitivity (DTH) reaction to dinitrofluorobenzene (DNFB) and splenocyte proliferation assays- It also is able to rescue the splenocytes of the apoptosis induced by stress. The capsaicin treatment increased the production of Th1 cytokines and decreased the production of Th2 cytokines and TGF-ß1 in the plasma and culture supernatants of immunosuppressed mice, which is associated with the modulation of Th2 induced by stress cells. Moreover, the production of corticosterone significantly decreased in capsaicin-treated animals as compared to control groups. The capsaicin treatment further attenuated the immunosuppression induced by the corticosterone treatment (40 mg/kg i.p. for 7 days), albeit less potently, as exhibited in the DTH response. Intriguingly, the capsaicin treatment decreased the induction of IL-10, IL-4, and TGF-ß1 through high doses of corticosterone, indicating direct cellular immunomodulation. These results show, that capsaicin is able to modulate chronic stress-induced immunosuppression, mediating corticosterone released inhibition, but also, that capsaicin significantly modulates the pharmacological action of corticosterone in vivo.

Immunomodulatory activity of Chilean Cyttaria species in mice with L5178Y lymphoma.

The immunomodulatory effect of hydrosoluble extracts of four Chilean Cyttaria species (Discomycetes, Fungi) was assessed in mice with L5178Y lymphoma. Oral administration of 100 mg extract per day for 7 days enhanced the percentual phagocytosis and phagocytosis index in animals receiving Cyttaria berteroi, Cyttaria darwinii, Cyttaria espinosae and Cyttaria harioti extracts. Differences in the digestion index were observed in mice treated with C. darwinii and C. berteroi. In the delayed-type hypersensitivity model, only C. harioti was able to modify the immune response. The results suggest that intake of Cyttaria can improve the immune system of consumers.

An experimental model of stress-induced immunosuppression produced by electrical stimulation of the brain in the rat.

The present paper reports a model of stress induction, based on electrical stimulation of the brain in normal Wistar rats. Stress-related stimulation of the hypothalamic-pituitary-adrenal axis produced a rise in circulating corticosterone levels that correlated significantly with the impairment of some immunological parameters, such as delayed hypersensitivity reactions to dinitrofluorobenzene and to sheep red blood cells, together with changes in splenocyte proliferation and phagocytic activity of peritoneal macrophages. This experimentally elicited stress in the rat is proposed as a suitable model of immunosuppression that could be used for the evaluation of drugs with potential immunomodulatory properties.

Phenytoin and electric shock-induced apoptosis in rat peripheral blood lymphocytes.

The apoptotic index (AI) of peripheral blood lymphocytes (PBL) and plasma corticosterone (CS) levels were determined in Wistar rats treated with phenytoin (PHT) at therapeutic and toxic doses (100 or 200 mg/kg/day, respectively, over a period of 7 days) and stressed by bifrontal electric shock (60 Hz/40 mA/0.2 seg). The values of CS and AI were found to be significantly higher in rats submitted to electric shock (ES) and in rats treated with therapeutic and toxic doses of PHT plus ES, than in rats treated only with PHT (P<0.001). The plasma concentrations of PHT were found to be significantly higher in rats treated with toxic doses than in those treated with therapeutic doses (P<0.001), while the control group (without treatment) and vehicle group (propilenglycol-ethanol-water, 40:10:50), showed low levels of CS, and less than 1% of AI. The DNA analysis by electrophoresis in agarose in all the groups was positive, displaying the ladder pattern characteristic of apoptotic process (200 bp), except in the control groups (no treatment and vehicle treated). Our results demonstrate that chronic stress, caused by ES, produces an elevation of CS. The values of apoptosis were correlated with the CS levels, suggesting that the apoptotic inductor process is a consequence of an increase in the concentration of corticosterone in plasma, in response to the hypothalamic-pituitary-adrenals (HPA) axis activation, while phenytoin at therapeutic doses is only a moderate apoptosis inductor.