Mechanism(s) of the potential protective effects of selected antioxidants against immunosuppression–induced by psychic stress in rats

Abstract

The immune system is normally present in homeostatic condition. Immunosuppression is accompanied by the increase of susceptibility to infection and/or cancer formation while, its over activity is linked with hypersensitivity or autoimmunity. Psychic stress is known to induce immunosuppression but the mechanism is still controversial and presents an area for scientific debates. It is believed that activation of the sympathetic nervous system or the hypothalamic pituitary-adrenal axis mechanisms are among the players in stress-induced immunosuppression but the literatures indicate other factors. Direct oxidative stress in the immune cells and organs is a suspect candidate but scientific evidence is needed to explore its role. The present study aims to elucidate a possible relationship between oxidative stress and cold-immobilization (as a model for psychic stress) induced-immunosuppression. Also to investigate the possible protective effect of melatonin and silymarin , as tools, so as to help understanding the underlying mechanism of psychic stress-induced immunosuppression. The present work involves two experiments. First experiment correlate the oxidative stress parameters such as thymus gland and spleen contents of GSH, MDA and NO, to immune relevant parameters such as thymus and spleen relative weights, lymphoproliferative response to PHA, Con-A and LPS as well as corticosterone as a marker for psychic stress. All as a function of time of cold-immobilization in rats. The second experiment investigates the possible protective effect of melatonin and silymarin (100mg/kg once daily for 5 consecutive days before stress) against psychic stress-induced immunosuppression. In addition to the previously mentioned parameters, macrophage function, apoptosis in splenocytes and host resistance to Listeria monocytogenes and Streptococcus pneumonia are assessed. Results of the present work show that cold-immobilization stress revealed a marked direct oxidative stress in the thymus and spleen as indicated by a marked decrease in GSH content accompanied by a marked elevation of MDA and NO contents. It also revealed a corresponding immunosuppression as shown by a significant inhibition in T-and Bcell proliferation, a marked decrease in macrophage function, induction of apoptosis in splenocytes and a marked decrease in host resistance to both Listeria monocytogenes and Streptococcus pneumonia. Both melatonin and silymarin revealed a significant preventive effects of all previously mentioned parameters with only difference in B-cell function where protective effect of melatonin was more obvious on T-cell rather than B-cell functions. In conclusion, it seems that oxidative stress plays an important role as a mechanism of acute psychic stress induced-immunosuppression that could be mitigated by the use of antioxidants.