title: Prolonged C1 inhibitor administration improves local healing of burn wounds and reduces myocardial inflammation in a rat burn wound model.
abstract: In a previous study, the authors found persistent presence of acute inflammation markers such as C-reactive protein and complement factors locally in burn wounds. This persistence of acute inflammation may not only delay local burn wound healing but also have a systemic effect, for instance on the heart. Here, the effects of C1 esterase inhibitor (C1inh), an inhibitor of complement activation, on burn wound progression and the heart were analyzed in rats. Dorsal full-thickness burn wounds (2 × 4 cm) were induced on female Wistar rats (n = 14). The rats were divided into two groups (n = 7): a control group (just burns) and a C1inh group. C1inh was administered daily intravenously for 14 days. The burn wound, healthy skin from the hind leg (internal control), and the heart were then fixed in formalin. Tissues were analyzed for granulation tissue formation, reepithelialization, amount and type of infiltrating inflammatory cells (granulocytes and macrophages), and inflammatory markers (complement factors C3 and C4). C1inh treatment significantly reduced the amount of granulation tissue and significantly increased reepithelialization. C1inh also significantly reduced macrophage infiltration. Burns induced infiltration of macrophages into the ventricles of the heart and remarkably also into the atria of the heart. This effect could be counteracted by C1inh. These data show that systemic treatment with C1inh acts at different levels resulting in improved healing locally in burn wounds and systemically reduced inflammation in the heart. Therefore, C1inh might be a possible therapeutic intervention for burn wound patients.
authors.affiliation: Department of Pathology, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Mark P V
authors.initials: MP
authors.lastname: Begieneman
authors.forename: Bela
authors.initials: B
authors.lastname: Kubat
authors.forename: Magda M W
authors.initials: MM
authors.lastname: Ulrich
authors.forename: Nynke E
authors.initials: NE
authors.lastname: Hahn
authors.forename: Yvette
authors.initials: Y
authors.lastname: Stumpf-Stolker
authors.forename: Miranda
authors.initials: M
authors.lastname: Tempelaars
authors.forename: Esther
authors.initials: E
authors.lastname: Middelkoop
authors.forename: Sacha
authors.initials: S
authors.lastname: Zeerleder
authors.forename: Diana
authors.initials: D
authors.lastname: Wouters
authors.forename: Marieke S
authors.initials: MS
authors.lastname: van Ham
authors.forename: Hans W M
authors.initials: HW
authors.lastname: Niessen
authors.forename: Paul A J
authors.initials: PA
authors.lastname: Krijnen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002056:Burns / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016009:Chi-Square Distribution; D003172:Complement C1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051056:Complement Inactivating Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000097:blood; D007262:Infusions, Intravenous; D015601:Injury Severity Score; D009205:Myocarditis / Q000097:blood / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D015996:Survival Rate; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D003172:Complement C1; D051056:Complement Inactivating Agents; D018836:Inflammation Mediators