It has been demonstrated in animal models and in humans that the hormones related during chronic stress can increase both an individual's susceptibility to viral infections and the pathology of an on-going infection. Specifically, stress elevates blood levels of glucocorticoids (Gcs), which down-regulate the expression of cellular adhesion molecules and pro-inflammatory cytokines. These actions inhibit the normal inflammatory response at the site of infection by preventing the appropriate activation and trafficking of mononuclear cells. However, recent data from our lab show that social reorganization (SRO) stress enhances lung inflammation in a murine model of influenza infection, despite the fact that plasma Gcs are significantly elevated. This stressor disrupts the established dominance hierarchy among the mice, and the elicits aggressive behavior. Fighting between male mice has been reported to elevate serum levels of nerve growth factor (NGF), and one of the aims of this proposal is to determine if SRO increases circulating NGF. Studies provide evidence that NGF may mediate the observed inflammation in two major ways, by stimulating lymphocyres via specific receptors and by counter-acting the anti-inflammatory actions of Gcs at a cellular and/or molecular level. We will test the hypothesis that lymphocyte GC receptors are down-regulated during SRO. In addition, the specific role of NGF in the progression of influenza infection will be determined in vivo by removing the source of NGF (salivary glands) prior to SRO and infection. These studies will advance understanding of the mechanisms by which stress can modulate the regulation of an immune response and negatively affect host health.
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