Activation of neuroendocrine responses by stress has been shown to suppress anti-viral immune responses, including natural resistance mechanisms and adaptive immunity. For example, elevated plasma corticosterone (Cort) levels, arising from activation of the hypothalamic-pituitary-adrenal (HPA) axis, have been shown to suppress mononuclear cell trafficking and cell- mediated immunity. In addition, increased tissue and circulating catecholamines (CAT), due to activation of the sympathetic nervous system (SNS), suppress activation of virus-specific CD8+ T-cells. Recent studies have shown that stress can also suppress activation of natural killer (NK) cell function during an influenza viral infection, and that the mechanism of suppression is independent of Cort or CAT. In preliminary studies, the opioid receptor antagonist naltrexone has been shown to block stress-induced suppression of NK activity during an influenza A/PR8 viral infection, suggesting that opioids may play an important immunomodulatory role in the resistance to viral infection. As it has been shown that opioids can modulate NK cell function, and that stress can activate opioid responses, this project was designed to investigate the immunomodulatory role of endogenous opioids during an acute viral infection of the respiratory track. An animal model of influenza will be used to dissect the mechanism by which opioids modulate NK responses.
