Anti-IFNG monoclonal antibody, clone 5T.C4 [Brilliant Violet 510]

Background: The pathogenesis of macrophage activation syndrome (MAS) is not clearly understood: a large body of evidence supports the involvement of mechanisms similar to those implicated in the setting of primary hemophagocytic lymphohistiocytosis. Objective: We sought to investigate the pathogenic role of IFN-gamma and the therapeutic efficacy of IFN-gamma neutralization in an animal model of MAS. Methods: We used an MAS model established in mice transgenic for human IL-6 (IL-6TG mice) challenged with LPS (MAS mice). Levels of IFN-gamma and IFN-gamma-inducible chemokines were evaluated by using real-time PCR in the liver and spleen and by means of ELISA in plasma. IFN-gamma neutralization was achieved by using the anti-IFN-gamma antibody XMG1.2 in vivo. Results: Mice with MAS showed a significant upregulation of the IFN-gamma pathway, as demonstrated by increased mRNA levels of Ifng and higher levels of phospho-signal transducer and activator of transcription 1 in the liver and spleen and increased expression of the IFN-gamma-inducible chemokines Cxcl9 and Cxcl10 in the liver and spleen, as well as in plasma. A marked increase in Il12a and Il12b expression was also found in livers and spleens of mice with MAS. In addition, mice with MAS had a significant increase in numbers of liver CD68(+) macrophages. Mice with MAS treated with an anti-IFN-gamma antibody showed a significant improvement in survival and body weight recovery associated with a significant amelioration of ferritin, fibrinogen, and alanine aminotransferase levels. In mice with MAS, treatment with the anti-IFN-gamma antibody significantly decreased circulating levels of CXCL9, CXCL10, and downstream proinflammatory cytokines. The decrease in CXCL9 and CXCL10 levels paralleled the decrease in serum levels of proinflammatory cytokines and ferritin. Conclusion: These results provide evidence for a pathogenic role of IFN-gamma in the setting of MAS.

Sedentary behavior increases the risk of many chronic disorders, in addition, these chronic diseases are associated with elevated markers interleukin-6 (IL-6). Increasing evidence indicates that physical activity can prevent chronic inflammatory disease. However, the effect of exercise on sedentary individuals with disparate basal serum IL-6 level was not well elucidated. In this study, the gene expression profile of GES12384 was downloaded from the Gene Expression Omnibus (GEO) database. This data set contained 12 sedentary middle-aged men (6 high IL-6 and 6 low IL-6 level), and their blood samples were taken in the pre-exercise period and at the end of 24 weeks of exercise. The differentially expressed genes (DEGs) of 24 weeks group were identified, followed by functional enrichment analysis. Subsequently, protein-protein interaction (PPI) network and transcription factors (TFs)-DEGs network were constructed. A total of 193 DEGs were identified between high and low IL-6 level in the 24 weeks group. Functional enrichment analysis showed that DEGs were mainly involved in African trypanosomiasis pathway. PPI network revealed that the hub genes included C-C motif chemokine receptor 7 (CCR7), hemoglobin subunit delta (HBD), and interferon gamma (IFNG). Subnetworks analysis indicated that these genes were relevant to immune response, and participated in African trypanosomiasis pathway. The TF targets network found that myocyte enhancer factor 2A (MEF2A) was a key regulatory factor. In conclusion, the inflammation-related genes (CCR7, HBD, and IFNG) in sedentary individuals could be affected by exercise, and the identified DEGs and TFs in this study promoted our understanding of exercise inhibited the development of chronic disease. [GRAPHICS] .