A New Surgical Model of Skeletal Muscle Injuries in Rats Reproduces Human Sports Lesions.

Skeletal muscle injuries are the most common sports-related injuries in sports medicine. In this work, we have generated a new surgically-induced skeletal muscle injury in rats, by using a biopsy needle, which could be easily reproduced and highly mimics skeletal muscle lesions detected in human athletes. By means of histology, immunofluorescence and MRI imaging, we corroborated that our model reproduced the necrosis, inflammation and regeneration processes observed in dystrophic mdx-mice, a model of spontaneous muscle injury, and realistically mimicked the muscle lesions observed in professional athletes. Surgically-injured rat skeletal muscles demonstrated the longitudinal process of muscle regeneration and fibrogenesis as stated by Myosin Heavy Chain developmental (MHCd) and collagen-I protein expression. MRI imaging analysis demonstrated that our muscle injury model reproduces the grade I-II type lesions detected in professional soccer players, including edema around the central tendon and the typically high signal feather shape along muscle fibers. A significant reduction of 30% in maximum tetanus force was also registered after 2 weeks of muscle injury. This new model represents an excellent approach to the study of the mechanisms of muscle injury and repair, and could open new avenues for developing innovative therapeutic approaches to skeletal muscle regeneration in sports medicine.

Therapeutic effect of urocortin and adrenomedullin in a murine model of Crohn's disease.

BACKGROUND AND AIMS: Urocortin 1 (UCN) and adrenomedullin (AM) are two recently discovered neuropeptides that, due to their distribution and binding to receptors in immune cells, have emerged as potential endogenous anti-inflammatory factors. Crohn's disease is a chronic debilitating disease characterised by a Th1 driven severe inflammation of the gastrointestinal tract. This study investigated the therapeutic effect of UCN and AM in a murine model of colitis. METHODS AND RESULTS: Treatment with UCN or AM ameliorated significantly the clinical and histopathological severity of the inflammatory colitis, abrogating body weight loss, diarrhoea, and inflammation, and increased the survival rate of colitic mice. The therapeutic effect was associated with downregulation of both inflammatory and Th1 driven autoimmune responses, including regulation of a wide spectrum of inflammatory mediators. In addition, partial involvement of interleukin 10 secreting regulatory cells in this therapeutic effect was demonstrated. Importantly, UCN or AM treatments were therapeutically effective in established colitis and avoided recurrence of the disease. CONCLUSIONS: This work identifies UCN and AM as two potent anti-inflammatory factors with the capacity to deactivate the intestinal inflammatory response and restore mucosal immune tolerance at multiple levels. Consequently, both peptides represent novel multistep therapeutic approaches for the treatment of Crohn's disease and other Th1 mediated inflammatory diseases.

Therapeutic approaches of vasoactive intestinal peptide as an immunomodulatory cytokine / Aproximaciones terapéuticas al péptido intestinal vasoactivo como una citocina inmunomoduladora

Vasoactive intestinal peptide (VIP) is a neuropeptide produced by the lymphoid cells, which exerts a wide spectrum of immunological functions controlling the homeostasis of immune system through different receptors expressed in various immunocompetent cells. During the last decade, VIP has been clearly identified as a potent anti-inflammatory factor, both in innate and adaptive immunity. In innate immunity, VIP inhibits the production of pro-inflammatory cytokines and chemokines from macrophages, microglia and dendritic cells. In addition, VIP reduces the expression of costimulatory molecules on the antigen-presenting cells, and therefore reduces the activation of antigen-specific CD4+ T cells. In terms of adaptive immunity, VIP promotes Th2-type responses, and reduces the pro-inflammatory Th1-type responses. Several of the molecular mechanisms involved in the inhibition of cytokine and chemokine expression, and in the preferential development and/or survival of Th2 effectors, are perfectly known. Therefore, VIP and its analogues have been recently proposed as very promising candidates, alternative to other existing treatments, for treating acute and chronic inflammatory and autoimmune diseases, such as septic shock, rheumatoid arthritis, multiple sclerosis, Parkinson’s disease, Crohn’s disease, or autoimmune diabetes. The aim of this review is firstly to update our knowledge of the cellular and molecular events relevant to VIP function on the immune system; and secondly to gather together recent data that support its role as a type 2 cytokine. Recognition of the central functions that VIP plays in cellular processes is focusing our attention on this «very important peptide» as exciting new candidates for therapeutic intervention and drug development (AU)

El Péptido Intestinal Vasoactivo (VIP) es un neuropéptido producido por diferentes células inmunitarias, con un amplio abanico de funciones implicadas en el control homeostático del sistema inmunitario. Estos efectos son llevados a cabo a través de varios receptores específicos expresados en distintas células inmunocompetentes. En la última década, se ha identificado a VIP como un potente factor anti-inflamatorio, tanto en la inmunidad innata como en la adquirida. En la inmunidad innata, VIP inhibe la producción de citocinas y quimiocinas proinflamatorias por macró- fagos, microglía y células dendríticas. Además, VIP reduce la expresión de moléculas coestimuladoras en las células presentadoras de antígeno, reduciendo así la estimulación antígeno-específica de células T. En cuanto a la inmunidad adquirida, VIP favorece las respuestas tipo Th2 frente a las proinflamatorias tipo Th1. Actualmente se conocen perfectamente muchos de los mecanismos moleculares y celulares implicados en esta regulación. Por lo tanto, se ha propuesto recientemente a VIP y análogos como candidatos muy prometedores, alternativos a terapias existentes, en el tratamiento de varias enfermedades autoinmunitarias e inflamatorias crónicas, tales como shock endotóxico, artritis reumatoide, esclerosis múltiple, enfermedad de Parkinson y de Crohn, y diabetes tipo I. El principal objetivo de esta revisión es primeramente actualizar nuestro conocimiento sobre los procesos celulares y moleculares relevantes en la función inmunitaria de VIP, y en segundo lugar, reunir todos los datos recientes que sustentan la hipótesis de que este «very important peptide» podría ser considerado una citocina tipo 2 candidato en el diseño futuro de nuevas terapias inmunomoduladoras (AU)