Modulation of the immune response by tachykinins

Neuro-immunology is becoming an increasingly important discipline of immunology. This review has examined the immunomodulatory function of one group of neuropeptides, the TK, particularly SP and NKA. These peptides are localized in primary afferent nerves which have been shown to innervate several immune organs. In addition, binding sites for the TK have been demonstrated in thymus, spleen and lymph node. Several immune cell types also express neurokinin receptors including human circulating lymphocytes with binding to the Th/i class predominating, murine T and B cells, a human T lymphoblastoid cell line, human monocytes, rabbit polymorphonuclear leucocytes and guinea-pig macrophages. The apposition of nerves with immune cells and receptors for neuropeptides thus produces an environment for interaction between the nervous and immune systems. Studies in vitro and, more recently, in vivo have examined how the TK regulate immune cell responses. The TK stimulate proliferation of T cells, enhance mitogen-induced release of cytokines including IFN-gamma, TNF-alpha, IL-1 and IL-6 from mononuclear cells and macrophages, enhance immunoglobulin secretion and affect cellular chemotaxis and phagocytosis. Studies in vivo have shown a role for TK in lymphocyte recirculation of sheep lymph nodes, reversal of stress-induced thymic involution and Ig production in both rat and mouse. Many of these effects appear to be mediated via NK-2 type receptors. To date, most of the work has involved studies in vitro, but the results from these are now being validated by studies in vivo where both the immune system and neuropeptides are able to interact at many anatomical sites. The complexities of the immune and the nervous systems mean that only a small number of potential interactions has been examined. Future studies can be expected to amplify these observations, especially with respect to the understanding of inflammatory and immune diseases in humans.