Premium
Episodic Binge Ethanol Exposure Impairs Murine Macrophage Infiltration and Delays Wound Closure by Promoting Defects in Early Innate Immune Responses
Author(s) -
Curtis Brenda J.,
Hlavin Sara,
Brubaker Aleah L.,
Kovacs Elizabeth J.,
Radek Katherine A.
Publication year - 2014
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12369
Subject(s) - wound healing , chemokine , macrophage inflammatory protein , medicine , immunology , monocyte , cathelicidin , saline , pharmacology , innate immune system , immune system
Background Exacerbation of cutaneous wound infections and delayed wound closure are frequent complications seen in alcohol exposed subjects who sustain injuries. We previously reported that acute alcohol exposure alters the early dermal inflammatory phase of wound healing and also several parameters of the proliferative wound healing phase in wounds from ethanol (EtOH)‐treated mice for several days or weeks after EtOH exposure. Hence, it is likely that the cumulative defects arising in the early phases of the wound healing process directly contribute to the increased complications observed in intoxicated patients at the time of injury. Methods C57 BL /6 mice were given intraperitoneal EtOH (2.2 g/kg body weight) or vehicle (saline) EtOH using our episodic binge EtOH exposure protocol (3 days EtOH, 4 days off, 3 days EtOH) to yield a blood alcohol concentration (BAC) of 300 mg/dl at the time of wounding. Mice were subjected to six 3 mm full‐thickness dorsal wounds and immediately treated topically with 10 μ l of sterile saline (control) or diluted Staphylococcus aureus corresponding to 1 × 10 4 CFU /wound. Wounds were harvested at 24 hours post injury to evaluate wound area, neutrophil and macrophage accumulation, and the protein levels of cytokines, interleukin‐6 (IL‐6), IL ‐1 β , and IL ‐10, and chemokines, macrophage inflammatory protein‐2 (MIP‐2) and MIP ‐1 α , monocyte chemotactic protein‐1 ( MCP ‐1), and keratinocyte‐derived chemokine (KC). The abundance and localization of cathelicidin‐related antimicrobial peptide ( CRAMP ) and the kallikrein epidermal proteases ( KLK 5 and KLK 7) were also determined. Results Compared to control mice, EtOH‐treated mice exhibited delayed wound closure, decreased macrophage accumulation, and impaired production of MIP ‐1 α . Furthermore, skin from EtOH‐treated mice demonstrated a reduction in the abundance of epidermal CRAMP and KLK 7. Conclusions These findings suggest that EtOH exposure hinders several distinct components of the innate immune response, including phagocyte recruitment and chemokine/cytokine and AMP production. Together, these effects likely contribute to delayed wound closure and enhanced infection severity observed in intoxicated patients.