Comparative Study of Senescent Th Biomarkers in Healthy Donors and Early Arthritis Patients. Analysis of VPAC Receptors and Their Influence.

Pro-inflammatory CD4+CD28- T cells are characteristic of immunosenescence, but also of several autoimmune/inflammatory diseases. Vasoactive intestinal peptide (VIP) acts as an anti-inflammatory and immunomodulatory mediator on these cells. Our objective was to study the mutual influence between senescent Th cells and VIP axis in early arthritis (EA), comparing with non-EA donors. We characterized the correlation between senescent Th cells and clinic parameters of EA as well as the behavior of senescent Th biomarkers by real-time PCR. Clinical data were systematically recorded at baseline and after 6 months of follow-up. The number of CD4+CD28- T cells measured by sorting is higher in patients who initially meet ACR classification criteria for rheumatoid arthritis (RA) compared to those who were classified as undifferentiated arthritis (UA). A slight positive correlation between EA CD4+CD28- T cells and CRP or ESR and a negative correlation with bone mineral density were found. Th senescent biomarkers in EA CD4+CD28- T cells were similar to donors, however some of them increased after 6 months of follow-up. VPAC receptors were analyzed by real-time PCR and immunofluorescence, and CD4+CD28- T cells showed higher expression of VPAC2 and lower of VPAC1, VPAC2 showing a significant increased expression in EA cells. Sorted CD4+CD28- T cells were in vitro expanded in presence of VIP, wherein VIP increased senescent biomarker CD27, while it diminished CD57 or NKG2 senescent biomarkers. Our study demonstrates for the first time the existence of a link between senescent Th cells and the VIP axis.

Fibroblast abnormalities in the pathogenesis of systemic sclerosis.

Systemic sclerosis (SSc) is a chronic systemic disease characterized by autoimmunity, vascular lesions and progressive fibrosis. The fibrotic component is dominant in SSc compared with other vascular or autoimmune diseases and determines its prognosis and therapeutic refractoriness. Fibroblasts are responsible for abnormal extracellular matrix accumulation. Studies in cultured SSc skin fibroblasts have facilitated the identification of potential pathways involved in their profibrotic phenotype. Profibrotic fibroblasts characterized by abnormal growth and extracellular matrix synthesis may differentiate or expand from normal resident fibroblasts. Recruitment of bone marrow-derived progenitors and transdifferentiation of different cell lineages might also be involved. Multiple factors and signaling pathways appear to be involved in the development or persistence of the SSc fibroblast phenotype. Although their relative relevance and interplay are unclear, aberrant TGF-ß signaling seems pivotal and constitutes the best characterized therapeutic target.

Effects of dietary supplementation with vitamin C or vitamin E on cardiac lipid peroxidation and growth performance in broilers at risk of developing ascites syndrome.

OBJECTIVE: To assess effects of high dietary amounts of vitamin C or vitamin E and oxidative stress on the heart and growth performance of broilers maintained at an altitude of 2,200 m above sea level. ANIMALS: 360 chicks (1-day-old broilers). PROCEDURE: Birds were randomly assigned to 3 groups (120 chicks/group). Each group of birds was fed a specific diet (control group, basal diet containing 12 mg of vitamin E (DL-alpha-tocopherol acetate)/kg of feed without additional ascorbic acid; vitamin E group, basal diet supplemented with 75 mg of vitamin E/kg of feed; and vitamin C group, basal diet supplemented with 400 mg of ascorbic acid/kg of feed) throughout the entire 7 weeks of the study. Feed consumption and body weight of chicks were recorded on a weekly basis. Nine randomly selected birds from each group were euthanatized each week. Remaining birds were euthanatized at the end of the study. Samples of cardiac tissues were obtained to measure thiobarbituric acid reactive substances (TBARS), an indicator of oxidative stress. RESULTS: Vitamin E-supplemented diets resulted in better growth performance, lower rates of feed conversion, and lower TBARS content. Vitamin C-supplemented diets resulted in lower feed consumption and lower rates of feed conversion. When used separately, neither of the vitamins had any effect on mortality attributable to ascites syndrome. CONCLUSION AND CLINICAL RELEVANCE: It is recommended that diets supplemented with vitamin C, vitamin E, or both be fed to broilers maintained at an altitude of 2,200 m above sea level to improve growth performance.