Fig. 4.

eNAMPT neutralization reduces pristane-induced murine lung inflammation. A/B. Pristane-exposed mice exhibited significant inflammatory injury reflected by several BAL, tissue and blood indices. For example, BAL protein levels and numbers of BAL inflammatory cells at Day 10 were significantly increased in pristane-exposed, IgG-treated mice compared to unexposed controls but significantly reduced in mice receiving the ALT-100 mAb. C. In contrast to BAL results, quantification of peritoneal lavage cells from pristane-challenged mice showed no significant effect of ALT-100 mAb compared to IgG control mice. D/E. Levels of proinflammatory cytokines IL-6 and IL-8 were observed in pristane-exposed mice compared to control mice. Consistent with the inflammation-reducing capacity for the ALT-100 mAb and similar to the reductions in plasma levels of eNAMPT (Fig. 2B), reductions in IL-6 and IL-8 were observed in ALT-100 mAb-treated mice. F/G. Inflammatory cell subsets in pristane-exposed lungs were examined by flow cytometry. Significant accumulation of Siglec 1-positive CD11b + Ly6C + monocytes in the lung was observed whereas CD45⁻CD31⁺ vascular endothelial cells were significantly reduced by pristane exposure. ALT-100 mAb-treated mice showed normalization of these cellular inflammatory parameters with reduced numbers of Siglec1-positive CD11b + Ly6C + monocytes and increased numbers of lung endothelial cells compared to pristane only or IgG-treated mice.