Anti-inflammatory neuropeptides: A new class of endogenous immunoregulatory agents

Abstract

Resolution of inflammation and induction of immune tolerance are essential to stabilize immune homeostasis and to limit the occurrence of exacerbated inflammatory and autoimmune conditions. Multiple mechanisms act together to ensure the re-establishment of immune homeostasis and maintenance of tolerance. The identification of endogenous factors that regulate these processes is crucial for the development of new therapies for inflammatory/autoimmune conditions. Neuropeptides produced during an ongoing inflammatory response emerged as endogenous antiinflammatory agents that participate in processes leading to the resolution of inflammation and maintenance of tolerance. Anti-inflammatory neuropeptides and hormones such as vasoactive intestinal peptide, urocortin, adrenomedullin, melanocyte stimulating hormone, ghrelin and cortistatin have beneficial effects in a variety of experimental inflammatory and autoimmune models. Their therapeutic effect has been attributed to their capacity to downregulate innate immunity, to inhibit antigen-specific T H 1-driven responses, and to generate regulatory T cells. Finally, some of these neuropeptides have been identified as mediators of innate defense acting as natural antimicrobial peptides. Here we present the research findings in the neuropeptide immunoregulatory field, and examine possible therapies based on anti-inflammatory neuropeptides and hormones as a new pharmacologic platform.

Ghrelin Gene Products in Acute and Chronic Inflammation

“…Real-time PCR analysis revealed the expression of ghrelin mRNA in human T cells (Dixit et al 2004;Hattori et al 2001), B cells, neutrophils, macrophages, monocytes, dendritic cells, natural killer cells, and several leukemic cell lines (Baatar et al 2011;Delgado and Ganea 2008;Dixit et al 2004;Hattori et al 2001). In addition, when activated, T cells also express the preproghrelin protein and produce and secrete both acylated and unacylated ghrelin (Baatar et al 2011;Dixit et al 2004).…”

Promiscuous Dimerization of the Growth Hormone Secretagogue Receptor (GHS-R1a) Attenuates Ghrelin-mediated Signaling

“…The GHS-R1a receptor is a G protein-coupled receptor (GPCR) belonging to class I of GPCRs (23,24). GPCRs, such as the GHS-R1a, have been found to cross-talk with other GPCRs and have been found to exist and function as dimers or even higher structure oligomeric complexes (25)(26)(27)(28).…”

Effects of pituitary adenylate cyclase activating polypeptide on CD4+/CD8+T cell levels after traumatic brain injury in a rat model

“…Possibly, PACAP inhibits the expression of IL-12 thereby preventing T cell proliferation, or PACAP inhibits FasL expression suppressing the apoptosis of CD4 + T cells. [20][21][22] In conclusion, our results indicate that PACAP is neuroprotective after TBI, partly through the regulation of circulating T cells. Table 2, Figure 4).…”