Nerves, Neuropeptides and Mucosal Immune Response

Summary

It is now clear that nerves and neurotransmitters play an important role in regulating inflammatory events in general and immunity specifically. Several lines of evidence suggest close connections and interactions between the nervous and immune systems. In the intestinal tract where large amounts of putative neurotransmitters are found, and increased levels of these neuropeptides, have been associated with immunologically related diseases in these tissues, such as Crohn’s disease, these interactions may best be approached. Our own studies have attempted to focus on two peripheral neuropeptides, somatostatin (SOM), and substance P (SP). We have examined the effects of these neuropeptides on lymphocyte proliferation in vitro and have shown that SP significantly enhanced, whereas SOM decreased DNA synthesis by lymphocytes from the spleen or Peyer’s patches. The most potent effect of neuropeptides on immunoglobulin synthesis in vitro was that of SP which produced an isotype (IgA) specific increase of some 300% over controls with Peyer’s patch cells. When SP or SOM were administered in vivo via miniosmotic pumps, both neuropeptides significantly enhanced cell proliferation and immunoglobulin synthesis (IgA). It appears that SOM (as it has been shown before) has a “dual” effect on lymphocytes depending on its concentration and/or experimental conditions. In addition natural killer (NK) activity of intestinal epithelial but not splenic lymphocytes was significantly enhanced by SP but not SOM. Subsequently we have shown that the neuropeptide effects on lymphocytes are mediated via specific receptors present on these cells. Peyer’s patch lymphocytes were shown to have more receptors for SP and SOM as compared to splenic lymphocytes. The Kd of binding was in the nM range and both T and B cells and their subsets bound neuropeptides equally. Furthermore, we and others have demonstrated structural associations between nerves and mucosal immune cells. Collectively this evidence forms the suggestion that the nervous and immune systems act in concert at least in the gastrointestinal tract.