Rheumatoid arthritis and the alpha-chemokine IP-10.

Interferon(IFN)-gamma-induced protein 10 (IP-10) and its receptor, CXCR3, appear to contribute to the pathogenesis of rheumatoid arthritis (RA). IP-10 has been detected in sera, synovial fluid (SF), and synovial tissue in RA patients. IP-10 is mainly expressed by infiltrating macrophage-like cells and fibroblast-like synoviocytes in RA synovium. The elevated expression of CXCR3 on T cells from SF has been associated with high levels of IFN-gamma, which suggest a preferential Th1 phenotype. A human phase II clinical trial using an anti-IP-10 monoclonal antibody (MDX-1100) for RA patients who had an inadequate response to methotrexate treatment has shown that blocking IP-10 significantly increased response rate compared to the placebo group, suggesting a possible therapeutic use in humans.

[A review on thyroid autoimmune disorders and HCV chronic infection]. / Rassegna su malattie tiroidee autoimmuni e infezione cronica da HCV.

Frequently, patients with hepatitis C virus (HCV) chronic infection have high levels of serum anti-thyroperoxidase and/or anti-thyroglobulin autoantibodies, ultrasonographical signs of chronic autoimmune thyroiditis, and subclinical hypothyroidism, in female gender, vs healthy controls, or hepatitis B virus infected patients. In patients with "HCV-associated mixed cryoglobulinemia" (MC+HCV), a higher prevalence of autoimmune thyroid disorders was shown not only compared to controls, but also compared to HCV patients without cryoglobulinemia. Patients with MC+HCV or with HCV chronic infection, show an higher prevalence of papillary thyroid cancer than in controls, in particular in patients with autoimmune thyroiditis. Patients with HCV chronic infection, or with MC+HCV, in presence of autoimmune thyroiditis, show higher serum levels of T-helper (Th)1 (C-X-C motif) ligand 10 (CXCL10) chemokine than patients without thyroiditis. Probably, HCV thyroid infection acts by upregulating CXCL10 gene expression and secretion in thyrocytes recruiting Th1 lymphocytes, that secrete interferon-gamma and tumor necrosis factor-alpha. These cytokines might induce a further CXCL10 secretion by thyrocytes, thus perpetuating the immune cascade, that may lead into the appearance of autoimmune thyroid disorders in genetically predisposed subjects. A careful monitoring of thyroid function and nodules are recommanded in HCV patients.

[The alpha chemokine "Interferon gamma-induced protein 10" (IP-10) in Graves' disease and Graves'ophthalmopathy]. / L'alfa chemochina "proteina 10 indotta dall'interferon-gamma" (IP-10) nel morbo di Graves e nell'oftalmopatia basedowiana.

Interferon(IFN)γ-induced protein 10 (IP-10) and its receptor, CXC receptor 3, appear to contribute to the pathogenesis of Graves' disease (GD) and Graves' ophthalmopathy (GO). Under the influence of IFN-γ, IP-10 is secreted by thyrocytes (in GD), fibroblasts and preadipocytes (in GO). Determination of high level of IP-10 in peripheral liquids is therefore a marker of a Th1 orientated immune response. Circulating IP-10 is associated with the active phase of GD in both newly diagnosed and relapsing hyperthyroid patients. Methimazole reduces IP-10 secretion by isolated thyrocytes, decreases serum IP-10 levels, and promotes a transition from Th1 to Th2 dominance in patients with GD active phase. In GD patients the decrease of IP-10 after thyroidectomy and radioiodine strongly suggests that this chemokine is mainly produced by the thyroid itself. In GO patients the increased concentrations of IP-10, at least in part, reflect the activity of orbital inflammation. A significant reductions in IP-10 serum concentrations during corticosteroids and or radiotherapy treatments, as compared both to control group and to basal values in GO patients, suggest that this chemokine could serve as a guideline in therapeutic decision-making in patients with GO. Further studies are needed to evaluate whether IP-10 is a novel therapeutic target in GD and GO.

[The alpha chemokine "Interferon gamma-induced protein 10" (IP-10) in Graves' disease]. / La chemochina alfa "Interferon gamma-induced protein 10" (IP-10) nel morbo di Graves.

The alpha chemokine Interferon gamma-induced protein 10 (IP-10) and its receptor, CXC receptor 3, appear to contribute to the pathogenesis of Graves' disease (GD) and Graves' ophthalmopathy (GO). Under the influence of Interferon-γ, IP-10 is secreted by thyrocytes (in GD), fibroblasts and preadipocytes (in GO). Determination of high level of IP-10 in peripheral liquids is therefore a marker of a Th1 orientated immune response. Circulating IP-10 is associated with the active phase of GD in both newly diagnosed and relapsing hyperthyroid patients. Methimazole reduces IP-10 secretion by isolated thyrocytes, decreases serum IP-10 levels, and promotes a transition from Th1 to Th2 dominance in patients in GD active phase. In GD patients the decrease of IP-10 after thyroidectomy and radioiodine strongly suggests that this chemokine is mainly produced by the thyroid itself. In GO patients the increased concentrations of IP-10, at least in part, reflect the activity of orbital inflammation. A significant reductions in IP-10 serum concentrations during corticosteroids and or radiotherapy treatments, as compared both to control group and to basal values in GO patients, suggest that this chemokine could serve as a guideline in therapeutic decision-making in patients with GO. Further studies are needed to evaluate whether IP-10 is a novel therapeutic target in GD and GO.

Hepatitis C virus and type 1 diabetes.

Hepatitis C virus infection and diabetes mellitus are two worldwide, major public health problems with increasing complication and mortality rates. Type 1 diabetes mellitus (T1D) is characterized by an autoimmune process leading to pancreatic beta cell destruction; only when the major part of pancreatic beta cells have been destroyed the diabetes become clinically manifest. At the basis of the development of the T1D there is an interplay among environmental factors, pancreatic beta cells, the innate and adaptive immune system, the genetic background and the comorbidities of the patient. Viral infections, including hepatitis C virus infection, may be one of the factors that can almost accelerate progression to diabetes, through different mechanisms.

3,5-diiodo-L-thyronine increases resting metabolic rate and reduces body weight without undesirable side effects.

Recently, it was demonstrated that 3,5-diiodo-L-thyronine (T2) stimulates the resting metabolic rate (RMR), and reduces body-weight gain of rats receiving a high-fat diet. The aim of this study is to examine the effects of chronic T2 administration on basal metabolic rate and body weight in humans. Two euthyroid subjects volunteered to undergo T2 administration. Body weight, body mass index, blood pressure, heart rate, electrocardiogram, thyroid and liver ultrasonography, glycemia, total cholesterol, triglycerides, free T3 (FT3), free T4 (FT4), T2, thyroid stimulating hormone (TSH) and RMR were evaluated at baseline and at the end of treatment. RMR increased significantly in each subject. After continuing the T2 treatment for a further 3 weeks (at 300 mcg/day), body weight was reduced significantly (p<0.05) (about 4 percent), while the serum levels of FT3, FT4 and TSH, were unchanged. No side effects were observed at the cardiac level in either subject. No significant change was observed in the same subjects taking placebo.