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Blockade of IgM-Mediated Inflammation Alters Wound Progression in a Swine Model of Partial-Thickness Burn

Sadeghipour, Hamed MD*†; Torabi, Radbeh MD†‡; Gottschall, James MD; Lujan-Hernandez, Jorge MD*; Sachs, David H. MD; Moore, Francis D. Jr MD*; Cetrulo, Curtis L. Jr MD

Journal of Burn Care & Research: May/June 2017 - Volume 38 - Issue 3 - p 148–160
doi: 10.1097/BCR.0000000000000459
Original Articles

In a mouse model, a second-degree burn elicits a severe inflammatory response that is mediated by circulating autoantibody specific for a neoantigen (nonmuscle myosin). Nonmuscle myosin is expressed by injured tissue, leading to amplified ulceration and scarring. We hypothesize that a synthetic peptide (N2) can mimic the neoantigen and competitively inhibit the autoantibody, decreasing inflammation, and reducing the extent of burn injury in a preclinical swine model of burn. Second-degree burns were created on young swine using brass cylinders, warmed to varying temperatures before skin contact. Animals were treated in double-blind fashion with normal saline, control peptide, or blocking peptide. Biopsies were taken at 2 hours, 1, 4, 7, and 14 days after burn injury. Burn wound healing parameters were assessed. Immunohistochemical staining for Ki-67, immunoglobulin (Ig)M, and interleukin (IL)-8 were also performed. N2 blocking peptide administration decreased dermal injury at 4 days with increased reepithelization, indicating more rapid healing. N2 normalized skin histology by 14 days and showed improved epidermal healing. Granulation tissue thickness was decreased, and there was an accompanying decrease in neutrophil infiltration. The basal layer of epidermis in N2-treated animals displayed more cells positive for Ki-67, suggesting a prompter regenerative capacity. Immunohistochemical staining demonstrated decreased deposition of immunoglobulin M and interleukin-8 after thermal injury in animals treated with N2 peptide, in comparison to controls. The findings of this study identify N2 blocking a specific inflammatory pathway, as a novel therapeutic approach, preventing the evolution of cutaneous burn injuries in a preclinical animal model.

From the *Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts; Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; and Department of Surgery, Division of Plastic and Reconstructive Surgery, Louisiana State University Health Sciences Center, New Orleans, Louisiana.

This project was supported by NIH SBIR 2R44GM076743 awarded to Decimmune, Inc., Cambridge, MA. Dr. Moore is a co-founder of Decimmune, Inc. and retains an equity interest.

Address correspondence to Francis D. Moore, Jr., MD, Division of General and GI Surgery, Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115. Email: fmoore@partners.org.

© 2017 The American Burn Association