Autonomic Regulation of Immunity

The sympathetic nervous system innervates the major lymphoid organs such as the spleen with nerve fibers reaching both the vasculature and the parenchyma where lymphocytes, primarily T cells (T helper type 1-2, T l, Tj 2), reside (Eriedman and Irwin, 1997). T cells possess receptors for both norepinephrine and neuropeptide Y that are released in response to sympathetic nerve stimulation. The adrenergic receptors are primarily the subtype, which is consistent with data demonstrating that p2 agonists can markedly influence the immune system (Kohm and Sanders, 2001). Eor example, stimulation of T cell receptors results in increased cyclic AMP formation, which can modulate cytokine expression, i.e., decreasing 

TNF-a and increasing IL-8 (Webster et al 2002). Consistent with this, selective receptor antagonists such as butox-amine can antagonize the corticotrophin-releasing factor-induced reduction in natural killer (NK) cell activity (Irwin et al., 1990). Sympathetic nerve stimulation also enhances Tj 2 cytokine production while inhibiting Tj l cytokine production. Thus, P2 receptor agonists can suppress interferon-y (IFN-y) production by Tj l cells, an effect, which can be blocked by propranolol. Interestingly, prion presence in the brain has been linked to an interaction between splenic monocytic cells and the sympathetic nervous system (Steinman, 2004). 

More recently it has become apparent that this relationship is reciprocal in nature, i.e., the immune system also can regulate the HPA axis and have significant effects on the CNS (see Carlson, 2003 Eskandari et al., 2003, for reviews). Chemo-kines, cytokines and other mediators released by the immune system can alter CNS function and abnormally high levels of some cytokines, such as IL-6, are associated with mental disorders, such as depression (see Chapter 34). In addition it is now clear that some neurohormones once thought to be exclusively neuronal are also produced by immune cells and that some immune system mediators are expressed by cells within the CNS. A consequence of this is that drugs whose primary site of action has classically been defined as the cen- 

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