The present work identifies hASCs as key regulators of immune tolerance, with the capacity to suppress T cell and inflammatory responses and to induce the generation/activation of antigen-specific regulatory T cells.

Cortistatin is a recently discovered cyclic neuropeptide related to somatostatin that has emerged as a potential endogenous antiinflammatory factor based on its production by, and binding to, immune cells. Crohn's disease is a chronic debilitating disease characterized by severe T helper 1 (Th1)-driven inflammation of the gastrointestinal tract. The aim of this study is to investigate the therapeutic effect of cortistatin in a murine model of colitis. Cortistatin treatment significantly ameliorated the clinical and histopathologic severity of the inflammatory colitis, abrogating body weight loss, diarrhea, and inflammation and increased the survival rate of the colitic mice. The therapeutic effect was associated with down-regulation of inflammatory and Th1-driven autoimmune response, including the regulation of a wide spectrum of inflammatory mediators. In addition, a partial involvement of regulatory IL-10-secreting T cells in this therapeutic effect was demonstrated. Importantly, cortistatin treatment was therapeutically effective in established colitis and avoided the recurrence of the disease. This work identifies cortistatin as an antiinflammatory factor with the capacity to deactivate the intestinal inflammatory response and restore mucosal immune tolerance at multiple levels. Consequently, cortistatin represents a multistep therapeutic approach for the treatment of Crohn's disease and other Th1-mediated inflammatory diseases.autoimmunity ͉ cytokines ͉ inflammation ͉ neuroimmunology

Alzheimer's disease (AD) is characterized by extracellular deposits of fibrillar beta-amyloid (Abeta) in the brain, increased microglial-mediated inflammatory reactions in senile plaques, selective neuronal death, and cognitive deficits. The use of agents that limit microglial activation and inflammation in AD has recently emerged as an attractive therapeutic strategy for this disease. The vasoactive intestinal peptide (VIP), a widely distributed neuropeptide, has shown neuroprotective effects in acute brain damage in vivo and potent anti-inflammatory actions in central nervous system. Here, we report that VIP inhibits Abeta-induced neurodegeneration by indirectly inhibiting the production of a wide panel of inflammatory and neurotoxic agents by activated microglia cells. The inhibitory effect of VIP is mediated by blocking signaling through the p38 MAPK, p42/p44 MAPK, and NFkB cascades, the three major transduction pathways involved in the transcription of inflammatory mediators and the production of free radicals by Abeta-activated microglia cells. Based on its neuroprotective action and its efficacy in inhibiting a broad range of inflammatory responses, VIP may provide a novel therapeutic approach to AD.

Background: Rheumatoid arthritis is a chronic autoimmune disease of unknown aetiology characterised by chronic inflammation in the joints and subsequent destruction of the cartilage and bone. Aim: To propose a new strategy for the treatment of arthritis based on the administration of cortistatin, a newly discovered neuropeptide with anti-inflammatory actions. Methods: DBA/1J mice with collagen-induced arthritis were treated with cortistatin after the onset of disease, and the clinical score and joint histopathology were evaluated. Inflammatory response was determined by measuring the levels of various inflammatory mediators (cytokines and chemokines) in joints and serum. T helper cell type 1 (Th1)-mediated autoreactive response was evaluated by determining the proliferative response and cytokine profile of draining lymph node cells stimulated with collagen and by assaying the content of serum autoantibodies. Results: Cortistatin treatment significantly reduced the severity of established collagen-induced arthritis, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect of cortistatin was associated with a striking reduction in the two deleterious components of the disease-that is, the Th1-driven autoimmune and inflammatory responses. Cortistatin downregulated the production of various inflammatory cytokines and chemokines, decreased the antigen-specific Th1-cell expansion, and induced the production of regulatory cytokines, such as interleukin 10 and transforming growth factor b1. Cortistatin exerted its effects on synovial cells through both somatostatin and ghrelin receptors, showing a higher effect than both peptides protecting against experimental arthritis. Conclusion: This work provides a powerful rationale for the assessment of the efficacy of cortistatin as a novel therapeutic approach to the treatment of rheumatoid arthritis.R heumatoid arthritis (RA) is an autoimmune disease that leads to chronic inflammation in the joints and subsequent destruction of the cartilage and erosion of the bone. Although the contribution of T helper cell type 1 (Th1) responses in RA is not completely understood, several studies in animal models point to a pathogenic role for Th1-derived cytokines. 1 2 Th1 cells reactive to components of the joint infiltrate the synovium, release proinflammatory cytokines and chemokines, and promote macrophage and neutrophil infiltration and activation. Inflammatory mediators, such as cytokines and free radicals, produced by infiltrating inflammatory cells, play a critical role in joint damage. 2 The fact that the inflammatory process in RA is chronic suggests that immune regulation in the joints is disturbed. Available therapies based on immunosuppressive agents inhibit the inflammatory component of RA and have the potential to slow progressive clinical disability by delaying erosions and deformity. 3 However, they neither reduce the relapse rate nor delay disease onset, and because continued treatment is required to maintain a beneficial effect, ...