Norepinephrine released after SNS activation also disturbs inflammatory cytokine networks by inhibiting production of immune-enhancing cytokines, such as IL-12 and TNF-α, and by upregulating production of inhibitory cytokines, such as IL-10 and TGF-β (Webster et al. 2002). Additionally, norepinephrine affects peripheral natural killer (NK) cells, a subset of lymphocytes that are a first-line defense against viral infections, tumor growth, and metastasis via their unique cytolytic action (Herberman and Ortaldo 1981). These cells carry receptors for norepinephrine (i.e., β-adrenergic receptors) on their surfaces (Madden et al. 1995). The cytolytic activity of NK cells involves the synergistic actions of the pore-forming protein perforin and the serine protease granzyme B to cause apoptosis of target cells (Graubert et al. 1996). Among the HPA hormones, gluco-corticoids and CRH both are potent inhibitors of NK-cell activity in vitro and in vivo. Hypothalamic CRH inhibits NK activity and IFN-γ production through actiavation of the SNS, which causes release of catecholamines (e.g., norepinephrine) from the spleen and activation of β-adrenergic receptors on NK cells (Irwin et al. 1990). Thus, it appears that the hormones secreted during stress
