Research Article Resolution of Sterile Inflammation: Role for Vitamin C Bassem M. Mohammed, 1,2 Bernard J. Fisher, 3 Quoc K. Huynh, 4 Dayanjan S. Wijesinghe, 5,6 Charles E. Chalfant, 5,6,7 Donald F. Brophy, 1 Alpha A. Fowler III, 3 and Ramesh Natarajan 3 1 Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, VA 23298-0533, USA 2 Department of Clinical Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt 3 Division of Pulmonary Disease and Critical Care Medicine, Department of Internal Medicine, Virginia Commonwealth University, P.O. Box 980050, Richmond, VA 23298-0050, USA 4 Department of Chemistry, Virginia Commonwealth University, Richmond, VA 23298, USA 5 Research Service, Hunter Holmes McGuire Veterans Administration Medical Center, Richmond, VA 23249, USA 6 Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA 23298, USA 7 he Massey Cancer Center, Richmond, VA 23298, USA Correspondence should be addressed to Ramesh Natarajan; rnataraj@vcu.edu Received 30 May 2014; Revised 29 July 2014; Accepted 31 July 2014; Published 9 September 2014 Academic Editor: Jos´ e C. Rosa Neto Copyright © 2014 Bassem M. Mohammed et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Introduction. Macrophage reprogramming is vital for resolution of acute inlammation. Parenteral vitamin C (VitC) attenuates proinlammatory states in murine and human sepsis. However information about the mechanism by which VitC regulates resolution of inlammation is limited. Methods. To examine whether physiological levels of VitC modulate resolution of inlammation, we used transgenic mice lacking L-gulono--lactone oxidase. VitC suicient/deicient mice were subjected to a thioglycollate-elicited peritonitis model of sterile inlammation. Some VitC deicient mice received daily parenteral VitC (200mg/kg) for 3 or 5 days following thioglycollate infusion. Peritoneal macrophages harvested on day 3 or day 5 were examined for intracellular VitC levels, pro- and anti-inlammatory protein and lipid mediators, mitochondrial function, and response to lipopolysaccharide (LPS). he THP-1 cell line was used to determine the modulatory activities of VitC in activated human macrophages. Results. VitC deiciency signiicantly delayed resolution of inlammation and generated an exaggerated proinlammatory response to in vitro LPS stimulation. VitC suiciency and in vivo VitC supplementation restored macrophage phenotype and function in VitC deicient mice. VitC loading of THP-1 macrophages attenuated LPS-induced proinlammatory responses. Conclusion. VitC suiciency favorably modulates macrophage function. In vivo or in vitro VitC supplementation restores macrophage phenotype and function leading to timely resolution of inlammation. 1. Introduction Resolution of inlammation typically follows an ordered series of events orchestrated by diferent cell types [1]. During the early stages of inlammation, leukocytes such as poly- morphonuclear neutrophils (PMN) are the irst immune cells to arrive at the site of inlammation. PMN are recruited by gradients of proinlammatory signals and usually reach peak numbers within 24–48 hrs. PMN have short half-lives and are normally cleared from sites of inlammation by undergoing apoptosis [2]. Mobilized monocyte-derived macrophages extravasate to inlammatory tissue sites and clear apoptotic PMN in a nonphlogistic fashion by the process of eferocyto- sis. Apoptotic PMN release “ind-me” signals that are sensed by extravasated macrophages [3]. Following phagocytosis, apoptotic PMN provides resolution cues to macrophages by evoking distinct signaling events that block release of proin- lammatory mediators thus allowing further engulfment of apoptotic cells. Mantovani et al. and Fleming and Mosser note that mobilized macrophages are divided into three groups based upon their activation states [4, 5]. hese include the M1, M2, and the recently described regulatory macrophages (M res ). M1 macrophages, classically referred to as activated macrophages, secrete proinlammatory factors that mediate Hindawi Publishing Corporation Mediators of Inflammation Volume 2014, Article ID 173403, 15 pages http://dx.doi.org/10.1155/2014/173403