• Yang Zhang, Xiaogang Zeng, Sha Chen, Zhujun Zhang, Peng Li, Weijing Yi, Hongtao Huang, Jing Yao, Shuhui Li, and Chuanmin Hu.
• Department of Clinical Biochemistry, Laboratory Sciences, the Third Military Medical University, Chongqing, Gaotanyan Street 30, Shapingba District, Chongqing 400038, PR China.
• Int. Immunopharmacol. 2011 Sep 1; 11 (9): 1333-40.

AbstractSepsis is characterized by uncontrolled inflammatory responses. Macrophage migration inhibitory factor (MIF) has been shown to play an important role in the progression of sepsis thus is a potential therapeutic target. The aim of this study is to produce IgG anti-MIF monoclonal antibodies (mAbs) with anti-septic abilities in vivo and to determine mechanisms of their function. We generated 8 IgG anti-MIF mAbs with high specificity and 3 of them showed potent protective abilities in murine lethal peritonitis induced by cecal ligation and puncture (CLP). One anti-MIF mAb, F11, showed 100% protection within 72 h after sepsis induction and 72% mice treated with this mAb survived up to 84 h with reduced lung and kidney pathology. F11 treatment also reduced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels in septic mice. We further found that all 8 anti-MIF mAbs recognized the same epitope located in the amino acid residue 1-20 region of the N terminus of the MIF protein. Three of the mAbs, F11 in particular, inhibited tautomerase activity in association with their protective effect on CLP mice. Thus, we have produced anti-MIF mAbs that protected mice from CLP-induced sepsis by recognizing the same epitope domains in MIF. These mAbs are promising candidates for further development of therapeutics against inflammatory diseases.Copyright © 2011 Elsevier B.V. All rights reserved.

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