Physiological crosstalk between melatonin and glucocorticoid receptor modulates T-cell mediated immune responses in a wild tropical rodent, Funambulus pennanti

Abstract

Immunoenhancing attributes of melatonin (Mel) on the immunocompromised state induced by glucocorticoid is well known, but the involvement of their receptors in the modulation of immunity has never been studied in any rodent. The present study explores the role of Mel and its receptors (MT1 and MT2) in amelioration of immunocompromised state induced by a synthetic glucocorticoid, dexamethasone (Dex) in a tropical rodent Funambulus pennanti. Immune parameters viz. DTH response, Lymphocyte proliferation, cytokine (IL-2) and antibody production were assessed following pretreatment of Mel and Dex alone or in combination. Mel enhanced the IL-2 production, thymic and splenic lymphocyte proliferation thereby increasing T helper cell associated immune responses and anti-KLH-IgG production. MT1 and MT2 receptor expression was downregulated following Dex treatment while glucocorticoid receptors (GR) expression was downregulated in Mel treated groups suggesting that the immunomodulatory effects of glucocorticoids and Mel are mediated via their receptors. To gain further insights on the role of Mel receptors, we used nonselective melatonin receptor antagonist luzindole which resulted in reversal of most of the immunomodulatory actions of Mel. Therefore, it may be suggested that a physiological cross talk exist between Mel and GR which is of high adaptive significance in wild animals for balancing the immunity during ecologically stressful conditions.