Summary 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‐γ, TNF‐α, 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.

The effects of surgical denervation, capsaicin, and 6-Hydroxydopamine pretreatment on the inflammatory response to thermal injury have been investigated in the rat. Surgical denervation and capsaicin pretreatment reduced the cellular and exudative reactions to the injury. 6-Hydroxydopamine appeared to have a selective effect on the exudative reaction only. The effects of surgical denervation are partly explained by local and systemic effects of the procedure.

1 Plasma extravasation was induced by electrical nerve stimulation and by perfusion of tachykinins over a vacuum-induced blister base on rat footpad. 2 Stimulation of the sciatic nerve (18 V, 15Hz, 0.5 ms) for 20min produced a significant increase in the protein content of the perfusate. The response in capsaicin pretreated rats was only 4% of the control response. This indicates that the electrically-induced plasma extravasation response was mediated by capsaicin-sensitive sensory fibres. 3 Exogenous perfusion of the mammalian tachykinins substance P, neurokinin A and neurokinin B and the non-mammalian tachykinins physalaemin, kassinin and eledoisin was used to determine the tachykinin receptor type mediating the plasma extravasation response. Dose-response curves of the tachykinins (10-9M-140M) gave a rank order of potency of substance P = phys- The rank order of potency and the greater potency of [Glp6, L-Pro9ISP6-over its D-isomer indicate an NK-1 neurokinin receptor mediates plasma extravasation in rat footpad skin.

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Summary Somatostatin inhibits in vitro lymphocyte prohferative responses from a variety of species including human, mouse and rat. The immunoinhibitory effects of somatostatin are thought to involve binding to specific cell surface .somatostatin receptors on immunocompetent cells. This report describes an IM vivo immunoinhibitory effect of somatostatin on the rat pophteal lymph node lymphocyte primary antibody response to sheep red blood cell (SRBC) stimulation. Infusion of somatostatin immediately following SRBC injection into the hind feet of rats had a dose-related inhibitory effect. At the highest concentration used, 10 nmol/L, the level of inhibition was similar to that previously described following neonatal capsaicin treatment of rats. This suggests that neonatal capsaicin treatment may lead to decreased primary antibody responses to SRBC by a selective effect on tachykinin containing nerves and a lesser effect on somatostatin containing nerves. Tbe immunoinhibitory effect of somatostatin was reversed by co-infusion of neurokinin A but not substance P, botb of which have been shown to stimulate tbis response. This suggests tbe possibility tbat multiple tacbykinin receptors are involved in the modulation of the SRBC primary antibody response in vii'O. These results present evidence for an in viuo immunomodulatory role of somatostatin.

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