The synergistic effect of ω3 and Vit D3 on glycemia and TNF-α in islet transplantation.

The current treatment of type 1 diabetes consists of insulin administration. Transplantation of islets of Langerhans is considered very favorable because the full effect of insulin treatment cannot be obtained in severe cases. Although agents such as omega-3 (ω3) and vitamin D3 (Vit D3) are known to contribute to the success of islet allo-transplantation (ITX), in this study we aimed to experimentally determine their effects on glycemia and TNF-α production. Wistar albino rats, which were used as recipients, were given ω3, Vit D3, and islets by gavage, and intraperitoneal- and intraportal injections, respectively. Daclizumab (DAC) was used for immunosuppression. Glycemia levels decreased in rats treated with ω3 and vit D3. TNF-α increased in all groups due to application of STZ. After ITX (day +1), the weakest increase was observed in the ω3 + Vit D3 group. In the ITX+DAC group, compared with that of ITX only, DAC was shown to decrease levels of TNF- α following ITX, only in control group, however, similar levels of TNF-α were observed in other groups. The values in the treated groups were already lower than those of the controls in the ITX group and also remained almost equal in the ITX+DAC group. We suggest that the use of ω3 and Vit D3 together will improve the pro-inflammatory aspect encountered during and after ITXs, and contribute to the reduction of the dose of immunosuppressants in these procedures.

Mechanisms of immunotherapy to wasp and bee venom.

Hymenoptera venoms are important allergens that can elicit both local and systemic allergic reactions, including life-threatening anaphylaxis. Venom immunotherapy (VIT) remains the most effective treatment, reducing the risk of systemic reactions in individuals with Hymenoptera venom allergy. VIT can restore normal immunity against venom allergens and provide patients with a lifetime of tolerance to venoms. During VIT, peripheral tolerance is induced by the generation of allergen-specific regulatory T (Treg) cells, which suppress proliferative and cytokine responses against the venom allergens. Treg cells are characterized by IL-10 secretion that directly or indirectly influence effector cells of allergic inflammation, such as mast cells, basophils and eosinophils. Treg cells also have influence on B cells, suppressing IgE production and inducing the production of blocking type IgG4 antibodies against venom allergens. An accumulating body of evidence suggests that Treg cells may affect allergen sensitization and methods for enhancing this cell population may eventually improve the efficacy of VIT. In this article, immune mechanisms enrolled in bee and wasp VIT are reviewed.

Peritransplant and long-term secretion of interleukin-1beta in cyclosporine treated syngeneic rats allografted with islets of langerhans.

Interleukin-1beta (IL-1beta) is one of the proinflammatory cytokines that may mediate primary nonfunction of islets of Langerhans, limiting the success of allogeneic transplantation. The aim of this study was to assess differences between the secretion of IL-1beta as well as glycemia in peri- and long-term periods of intraportal islet allo-transplantation with or without cyclosporine (CyA) immunosuppression. Inbred Wistar albino rats were transplanted intraportally with rat islets isolated by collagenase digestion. The two recipient groups (6 rats/group) were: group 1, control, islet transplantation (ITX) without any treatment and group 2, CyA-treated via the femoral muscle on days -1, 0, +1, and +2. Serum IL-1beta (pg/mL) levels were measured by ELISA on days 0 (pre-ITX), +1, +2, and +195. Tail vein blood was used to evaluate glycemia (mg/dL). No major differences were observed in IL-1beta secretion on days 0, +1, or +195 between the groups. Immunosuppressive treatment produced significantly lower secretion in group 2 (P < .002) on day +2. Significantly greater secretions were detected at days +195, +1, and +195 compared to days 0, +2, and +2, respectively (P < .002; P < .008; P < .002). Positive correlations were observed between IL-1beta levels on days +1 and +2 (r = 0.845, P < .034). The mean values in groups 1 and 2 on days 0, +1, and +2 were 140.6 +/- 4.62 vs 119.1 +/- 12.12, 73.1 +/- 19.59 vs 88.3 +/- 14.08, 106.5 +/- 13.79 vs 92.5 +/- 15.8, respectively. No animal in group 1 displayed glycemia while three group 2 animals did at day +195. However, a negative correlation was found between IL-1beta on day 0 and glycemia on day +195 (r = -0.999, P < .026). Our results suggest that IL-1beta secretion, which is detrimental for islet engraftment, decreases at peritransplant day +2, but is upregulated during long-term graft survival both in controls and in CyA-treated recipients.