C1 Inhibitor Administration Reduces Local Inflammation and Capillary Leakage, Without Affecting Long-term Wound Healing Parameters, in a Pig Burn Wound Model

Author(s): Halil Ibrahim Korkmaz*, Magda M.W. Ulrich, Wessel N. Van Wieringen, Hatice Doǧan, Marcel Vlig, Reindert W. Emmens, Klaas W. Meyer, Paul Sinnige, Sacha Zeerleder, Diana Wouters, Marieke S. Van Ham, Paul P.M. Van Zuijlen, Paul A.J. Krijnen, Hans W.M. Niessen

Journal Name: Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Formerly Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents

Volume 20 , Issue 2 , 2021


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Graphical Abstract:


Abstract:

Background: Burns induce a boost in local and systemic complement levels as well as immune cell infiltration in the burn wound, which may negatively affect wound healing.

Objective: In this study, the effects of long-term treatment with complement inhibitor C1 esterase inhibitor (C1inh) on post-burn inflammation and wound healing parameters were analyzed in time up to 60 days post-burn.

Methods: Burned pigs were treated either with or without C1inh up to 15 days post-burn. Burn wound biopsies and blood were collected at different time points up to 60 days post-burn. Thereafter, complement in blood as well as complement and immune cells in the wound, capillary leakage, necrosis, reepithelialization and wound contraction were quantified.

Results: No significant differences in complement C3 blood levels were observed at any time point between C1inh-treated and control pigs. In the wound, complement C4 levels were significantly lower in the C1inh group than in controls at day 3-6 and 21-30 post-burn. Similarly, C3 levels, neutrophil and macrophage infiltration in the wound were, although not statistically significant, reduced in C1inh-treated pigs at day 9-14 post-burn. No differences in lymphocyte infiltration in the wound were found between C1inh and control pigs. C1inh-treated pigs also showed reduced capillary leakage. Despite these effects, no significant differences in the long-term wound healing parameters necrosis, reepithelialization and wound contraction were observed between C1inh and control pigs.

Conclusion: In pigs, 15 days of C1inh treatment after burn, leads to a reduction in local inflammation and capillary leakage in the burn wound without affecting long-term wound healing parameters.

Keywords: C1 inhibitor, complement, inflammation, capillary leakage, burn wound, wound healing, pig burn wound model.

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Article Details

VOLUME: 20
ISSUE: 2
Year: 2021
Published on: 01 July, 2020
Page: [150 - 160]
Pages: 11
DOI: 10.2174/1871523019666200702101513
Price: $65

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