Anti-CXCL8 monoclonal antibody

Background and Aims. CD14(+) mononuclear phagocytes [MNPs] and T cells infiltrate colon in ulcerative colitis [UC]. Here we investigated how CD14(+) MNPs and the cytokines they produce shape the colonic effector T cell profile. Methods. Colonic or mesenteric lymph node [mLNs] CD4(+)T cells isolated from UC or Crohn's disease [CD] patients were stimulated with cytokines or autologous CD14(+) MNPs. Cytokine expression was assessed by intracytoplasmic staining and multiplex ELISA. Unsupervised phenotypic multicolour analysis of colonic CD14(+) MNPs was performed using the FlowSOM algorithm. Results. Among CD14(+)CD64(+)HLA-DR+SIRP alpha(+) MNPs, only the pro-inflammatory cytokine-producing CD163-subpopulation accumulated in inflamed UC colon and promoted mucosal IL-1 beta-dependent Th17,Th17/Th1,Th17/Th22 but not Th1 responses. Unsupervised phenotypic analysis of CD14(+)CD64(+) MNPs segregated CD163(-) monocyte-like cells and CD163(+) macrophages. Unexpectedly, IL-12, IL-1 beta and CD163(-), but not CD163(+), cells induced IL-8 expression in colonic CD4(+)T cells, which co-expressed IFN-gamma and/or IL-17 in UC and not CD. The CD163(-) monocyte-like cells increased the frequency of IL-8(+)IL-17(+/-)IFN-gamma T+/- cells through IL-1 beta and IL-12. Finally, colonic IL-8(+) T cells co-expressing GM-CSF, TNF-alpha and IL-6 were detected ex vivo and, promoted by IL-12 in the mucosa and mLNs in UC only. Conclusions. Our findings established a link between monocyte-like CD163-MNPs, IL-12, IL-1 beta and the detection of colonic memory IL-8-producing CD4(+) T cells, which might all contribute to the pathogenesis of UC.

This study examines different factors influencing the 13-valent pneumococcal conjugate vaccine (PCV13) specific antibody response in 8-13 months old Danish children starting in day care. We present secondary findings to the ProbiComp study, which included nose swabs, buccal swabs and blood samples from the children before entering day care (baseline) and again after 6 months. Pneumococci isolated from nose swabs were identified by latex agglutination kit and Quellung reaction. Luminex-based assay was used for antibody measurements against specific anti-pneumococcal capsular IgG. Buccal gene expression was analyzed by qPCR. Statistical analyses were performed in R and included Pearson's Chi-squared test, Welch two sample t-test and linear regression models. The PCV13 antibody response was unaffected by whether the children were carriers or non-carriers of any pneumococcal serotype. Having siblings increased the risk of carrying serotype 21 before day care (p=0.020), and having siblings increased the PCV13 antibody response at the end of study (p=0.0135). Hepatitis B-vaccination increased the PCV13 antibody response before day care attendance (p=0.005). The expression of IL8 and IL1B was higher in children carrying any pneumococcal serotype at baseline compared to non-carriers (p=0.0125 and p=0.0268 respectively).