Anti-IL17A monoclonal antibody, clone 4H6

Hypertension is now considered as an inflammatory disease, and the kidney is a key endorgan target. Experimental and clinical studies suggest that interleukin 17A (IL-17A) is a promising therapeutic target in immune and chronic inflammatory diseases, including hypertension and kidney disease. Elevated circulating IL-17A levels have been observed in hypertensive patients. Our aim was to investigate whether chronically elevated circulating IL-17A levels could contribute to kidney damage, using a murine model of systemic IL-17A administration. Blood pressure increased after 14 days of IL-17A infusion in mice when compared with that in control mice, and this was associated to kidney infiltration by inflammatory cells, including CD3(+) and CD4(+) lymphocytes and neutrophils. Moreover, proinflammatory factors and inflammatory-related intracellular mechanisms were upregulated in kidneys from IL-17A-infused mice. In line with these findings, in the model of angiotensin II infusion in mice, IL-17A blockade, using an anti-IL17A neutralizing antibody, reduced kidney inflammatory cell infiltrates and chemokine overexpression. In kidney biopsies from patients with hypertensive nephrosclerosis, IL-17A positive cells, mainly Th17 and gamma delta T lymphocytes, were found. Overall, the results support a pathogenic role of IL-17A in hypertensive kidney disease-associated inflammation. Therapeutic approaches targeting this cytokine should be explored to prevent hypertension-induced kidney injury.

Background: Prior Influenza A viral (IAV) infection has been shown to increase susceptibility to tuberculosis (TB) and TB has also been shown to be a primary cause of death during pandemics, including the Spanish Influenza outbreak of 1918-1919. The majority of data has been obtained from mouse models, thus the aim of this study was to determine the impact of Flu co-infection on host immunity and disease severity in TB patients at diagnosis. Methods: Sputum from 282 patients with active TB were analyzed for presence of FluA/FluB RNA at presentation using multiplex PCR. Sputum RNA was also analyzed for Mycobacterium tuberculosis (Mtb) load using S-16 RNA amplification. Supernatants from digested sputum and Mtb antigen-stimulated whole blood were analyzed using multiplex cytokine arrays and PBMC were analyzed for cytokine production from CD4+ T, CD8+ T and Mucosal Associated Invariant T cells (MAITs). Results: 12 (4.3%) of TB patients were found to have FluA or FluB viral RNA present in their sputum at the time of TB diagnosis. The TB/Flu co-infected patients had a significantly higher bacterial load compared to those with TB mono-infection (p = 0.0026). They had lower levels of IL17A in ex vivo sputum (p = 0.0275) and higher MCP-1 (CCL2) levels in the blood following PPD stimulation (p = 0.0267). TB/Flu co-infected subjects had significantly higher IFN-gamma+IL-17+CD4+ and IFN-gamma+IL-17-CD8+ cells compared to TB mono-infected subjects. Conclusions: These data show that Flu co-infection at time of TB diagnosis is associated with a higher bacterial load and differential cellular and soluble profiles. These findings show for the first time the impact of TB/Flu co-infection in a human cohort and support the potential benefit of Flu vaccination in TB-endemic settings.