vasoactive-intestinal-peptide and Gram-Negative-Bacterial-Infections

Gram negative sepsis remains a high cause of mortality and places a great burden on public health finance in both the developed and developing world. Treatment of sepsis, using antibiotics, is often ineffective since pathology associated with the disease occurs due to dysregulation of the immune system (failure to return to steady state conditions) which continues after the bacteria, which induced the immune response, have been cleared. Immune modulation is therefore a rational approach to the treatment of sepsis but to date no drug has been developed which is highly effective, cheap and completely safe to use. One potential therapeutic agent is VIP, which is a natural peptide and is highly homologous in all vertebrates. In this review we will discuss the effect of VIP on components of the immune system, relevant to gram negative sepsis, and present data from animal models. Furthermore we will hypothesise on how these studies could be improved in future and speculate on the possible different ways in which VIP could be used in clinical medicine.

Topics: Animals; Disease Models, Animal; Gram-Negative Bacterial Infections; Humans; Immune System; Inflammation; Lipopolysaccharides; Sepsis; Vasoactive Intestinal Peptide

The aim of the present study was to investigate potential interrelationships between immune and neural elements of Peyer's patches in normal pigs (n=8) and in pigs infected experimentally with Brachyspira hyodysenteriae and suffering from swine dysentery (n=8). Assessment of tissue concentration of neuropeptides by enzyme linked immunosorbent assay revealed increased levels of galanin (GAL) and substance P (SP) in samples from the infected animals. In contrast, concentrations of vasoactive intestinal polypeptide (VIP) and somatostatin (SOM) were similar in both groups. Immunohistochemistry demonstrated reactivity of nerve fibres with antibodies specific for dopamine β hydroxylase, vesicular acetylcholine transporter, SOM, GAL, VIP and SP in the interfollicular region and peripheral areas of the Peyer's patch lymphoid follicles. In the dysenteric pigs, the GAL-positive nerve fibres were more numerous and more intensely labelled than those in the normal animals. Flow cytometry revealed a decreased percentage of CD21(+) lymphocytes and lymphocytes expressing T-cell receptor (TCR)-γ, with or without CD8 (TCR-γ(+)CD8(-) and TCR-γ(+)CD8(+)), in the dysenteric pigs as compared with the normal animals. Percentages of other lymphocyte subsets (CD2(+), CD4(+), CD5(+), CD8(+), CD5(-)CD8(+)) were comparable between the groups. Immunohistochemical investigations generally correlated with results obtained by flow cytometry related to lymphocyte subpopulations. Swine dysentery can therefore affect neuroimmunomodulatory processes in the ileal Peyer's patch, in addition to the large intestine. GAL and SP may play a specific role in this neuroimmune cross-talk.

Topics: Animals; Brachyspira hyodysenteriae; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Galanin; Gram-Negative Bacterial Infections; Ileum; Immunohistochemistry; Lymphocyte Subsets; Peyer's Patches; Somatostatin; Substance P; Swine; Swine Diseases; Vasoactive Intestinal Peptide