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Uveitis is a sight-threatening inflammatory disease of the eye which represents the third leading cause of blindness in the developed countries. The conventional pharmacological treatment includes corticosteroids and immunosuppressive agents, which are limited by their side effects. New therapeutic strategies are thus strongly needed. Exogenously-administered carbon monoxide (CO) may represent an effective treatment for conditions characterized by a dysregulated inflammatory response. Carbon monoxide-releasing molecules (CORMs) are a novel group of compounds capable of carrying and liberating controlled quantities of CO. Among CORMs, CORM-A1 represents the first example of water soluble CO releaser. We show here that CORM-A1 under a late prophylactic regime is able to significantly ameliorate the natural course of experimental autoimmune uveoretinitis, a rodent model of immunoinflammatory posterior uveitis. The present study strongly supports the development of CORM-A1 as a potential new drug for treatment of patients with non-infectious posterior uveitis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

HE3286 (17alpha-ethynyl-5-androstene-3beta, 7beta, 17beta-triol) is a synthetic derivative of a natural anti-inflammatory steroid, beta-AET (5-androstene-3beta, 7beta, 17beta-triol). HE3286 is orally bioavailable and treats established disease in models of ulcerative colitis, collagen-induced arthritis, and collagen antibody-induced arthritis, reducing clinical signs of disease and proinflammatory signals, including IL-6 and matrix metallopeptidase 3. HE3286 modulates nuclear factor kappaB through an unknown mechanism but does not interact with any of the steroid-binding nuclear hormone receptors and is not immune suppressive. HE3286 was safe and well tolerated in phase I studies and is under evaluation in multicenter phase I/II clinical trials for ulcerative colitis and arthritis. HE3286 may provide a new treatment option for patients with inflammatory and autoimmune diseases.

5-Androsten-3beta, 17beta-diol (HE2100), and a synthetic analogue HE3204 are regarded as immune-regulating hormones, because both induce changes in the reporter antigen-popliteal lymph node assay (RA-PLNA). Mice were injected in the footpad with either HE2100 or HE3204 (0.01-3 mg), and a nonsensitizing dose of trinitrophenyl ovalbumin (TNP-OVA) was used as bystander reporter antigen. Seven days later, nodes were removed and numbers of cells (CD3, CD4, CD8, CD19; flow cytometry), TNP-specific IgM, IgG1, and IgG2a antibody-forming cells (AFCs; ELISPOT assay), and cytokines (interleukin-4 [IL-4], interferon-gamma [IFN-gamma]; ELISA) were measured. HE2100 and HE3204 increased cell numbers in a dose-dependent fashion. T (helper and suppressor) cells and B cells were increased (>5-fold). HE3204 was apparently twice as potent as HE2100. Both increased the B/T ratio (fivefold), increased TNP-specific IgM and IgG1 ( approximately 50-fold), and induced IgG2a AFCs. Both increased IL-4 and IFN-gamma secretion (up to threefold). Both displayed anti-inflammatory activity in the murine model of carrageenan-induced pleurisy, as evidenced by reduced neutrophil numbers and exudate volumes. Our observations suggest that both HE2100 and HE3204 are immune-regulating steroid hormones that exhibit anti-inflammatory properties. HE2100 (1 mg/mouse per day) provided significant benefit when given at disease onset in the SJL/J female mouse model of experimental autoimmune encephalomyelitis. These compounds and their analogues are candidates for further testing in autoimmune diseases.

The observation of neurological dysfunctions resembling multiple sclerosis (MS) seen clinically and/or by MRI in patients with celiac disease has focused attention on the possibility that cryptic gluten sensitivity may be involved in the pathogenesis of MS. Here we study the effects of a gluten-free diet on the course of protracted-relapsing EAE in DA rats, serving as a preclinical model of human MS. The data show not only that this nutritional approach failed to ameliorate development of the disease but rather that it exacerbated the course.

Beta-glucans are naturally occurring polysaccharides that exert important immunostimulatory activities. In the present study, we evaluated whether beta-glucans could modulate the development and the course of systemic lupus erythematosus (SLE). To this aim, we employed the classical model of SLE represented by the F1 hybrid between the NZB and NZW mouse strains which develop severe lupus-like phenotypes comparable to that of SLE patients. The administration of beta-glucan was associated to a more aggressive development of the disease and a worse prognosis, as observed from the clinical, biochemical and histopathological data. This finding implies that restraint should be practised in the possible use of beta-glucans as immunomodulators in human therapy in the context of SLE. [ABSTRACT FROM AUTHOR]

The transferrin (Tf) family of iron binding proteins includes important endogenous modulators of the immune function that may modulate autoimmune diseases. To define more clearly the role of apotransferrin (apoTf) in type 1 diabetes we determined the impact of this protein on type 1 diabetes as investigated in islet cells, animal models and patient sera. First, we demonstrated that recombinant apoTf counteracts the cytokine-induced death of murine pancreatic islet cells. Secondly, human apoTf administration favourably influences the course of type 1 diabetes in animal models, resulting in protection against disease development that was associated with reduction of insulitis and reduced levels of proinflammatory cytokines. Finally, we confirmed that patients with newly diagnosed type 1 diabetes manifest significantly lower apoTf serum levels compared to healthy controls and patients with long-lasting disease. In conclusion, our data suggest the apoTf pivotal role in the perpetuation of type 1 diabetes pathology. [ABSTRACT FROM AUTHOR]