Treatment of Paraquat-Induced Lung Injury With an Anti-C5a Antibody: Potential Clinical Application*

Sun, Shihui; Jiang, Yuting; Wang, Renxi; Liu, Chenfeng; Liu, Xiaoling; Song, Nianping; Guo, Yan; Guo, Renfeng; Du, Lanying; Jiang, Shibo; Li, Yan; Qiu, Zewu; Zhao, Guangyu; Zhou, Yusen

Complement activation products C5a play an important role in proinflammatory responses. To determine whether IFX-1 could alleviate the clinical signs of paraquat poisoning, we compared hemograms, C-reactive protein (CRP), ALT, BUN, CRE concentrations, and the prothrombin time (PT) in IFX-1-treated (or not) cynomolgus macaques at 16 hours post paraquat administration. We found that the number of lymphocytes and eosinophils decreased significantly after paraquat administration, whereas the number of neutrophils and monocytes increased. Surprisingly, in contrast to the sham treatment group, the IFX-1 treatment group had fewer neutrophils (p < 0.001) and monocytes (p < 0.05) at 16 hours post paraquat administration. Compared with the sham treatment group, the IFX-1-treated group showed a sharp decrease in CRP, CRE, BUN, ALT, and AST levels, suggesting that IFX-1 reduced acute systemic inflammatory responses induced by paraquat. In addition, IFX-1 shortened the PT (p < 0.05), indicating that the antibody also inhibited the coagulation cascade (Supplemental Fig. 4 , Supplemental Digital Content 6, http:// links.lww.com/CCM/D164; legend, Supplemental Digital Content 1, http://links.lww.com/CCM/D159). Coagulation abnormality has been suggested as one of the prognostic factors for ALI/acute respiratory distress syndrome (32, 33).