Rabbit Anti-IL17F Polyclonal antibody

The current study sought to delineate the gene expression profile of the host response in the caecum and colon during acute infection with Clostridium difficile in a mouse model of infection, and to investigate the nature of the unfolded protein response in this process. The infected mice displayed a significant up-regulation in the expression of chemokines (Cxcl1, Cxcl2 and Ccl2), numerous pro-inflammatory cytokines (Ifng, Il1b, Il6, and Il17f), as well as Il22 and a number of anti-microbial peptides (Defa1, Defa28, Defb1, Slpi and Reg3g) at the site(s) of infection. This was accompanied by a significant influx of neutrophils, dendritic cells, cells of the monocyte/macrophage lineage and all major subsets of lymphocytes to these site(s). However, CD4 T cells of the untreated and C. difficile-infected mice expressed similar levels of CD69 and CD25. Neither tissue had up-regulated levels of Tbx21, Gata3 or Rorc. The caeca and colons of the infected mice showed a significant increase in eukaryotic initiation factor 2 (eIF2) phosphorylation, but neither the splicing of Xbp1 nor the up-regulation of endoplasmic reticulum chaperones, casting doubt on the full-fledged induction of the unfolded protein response by C. difficile. They also displayed significantly higher phosphorylation of AKT and signal transducer and activator of transcription 3 (STAT3), an indication of pro-survival signalling. These data underscore the local, innate, pro-inflammatory nature of the response to C. difficile and highlight eIF2 phosphorylation and the interleukin-22-pSTAT3-RegIII axis as two of the pathways that could be used to contain and counteract the damage inflicted on the intestinal epithelium.

AIMS To assess safety, pharmacokinetics (PK) and clinical efficacy of bimekizumab (formerly UCB4940), a novel humanized monoclonal antibody and dual inhibitor of interleukin (IL)-17A and IL-17F, in subjects with mild plaque psoriasis. METHODS Randomized, double-blind, first-in-human study of bimekizumab in 39 subjects who received single-dose intravenous bimekizumab (8-640 mg) or placebo (NCT02529956). RESULTS Bimekizumab demonstrated dose-proportional linear PK and was tolerated across the dose range assessed. No subject discontinued due to treatment-emergent adverse events and no severe adverse events were reported. Bimekizumab demonstrated fast onset of clinically-meaningful effects on skin of patients with mild psoriasis as early asWeek 2. Maximal improvements (100% or near 100% reductions from baseline) in all measures of disease activity were observed between Weeks 8-12 in subjects receiving 160-640 mg bimekizumab. The duration of effect at doses >= 160mg was evident up toWeeks 12-20 after a single intravenous dose, dependent on endpoint. CONCLUSIONS This is the first study to demonstrate the safety, tolerability and clinical efficacy of a dual IL-17A and IL-17F inhibitor, in subjects with mild psoriasis. Bimekizumab showed fast onset of clinically-meaningful efficacy by Week 2, with a maximal or near-maximal magnitude of response that was maintained up to studyWeeks 12-20. These findings support the continued clinical development of bimekizumab for diseases mediated by both IL-17A and IL-17F, including psoriasis.