Wound Trauma Mediated Inflammatory Signaling Attenuates a Tissue Regenerative Response in MRL/MpJ Mice

Abstract

Background: Severe trauma can induce pathophysiological responses that have marked inflammatory components. The development of systemic inflammation following severe thermal injury has been implicated in immune dysfunction, delayed wound healing, multi-system organ failure and increased mortality. Methods: In this study, we examined the impact of thermal injury-induced systemic inflammation on the healing response of a secondary wound in the MRL/MpJ mouse model, which was anatomically remote from the primary site of trauma, a wound that typically undergoes scarless healing in this specific strain. Ear-hole wounds in MRL/MpJ mice have previously displayed accelerated healing and tissue regeneration in the absence of a secondary insult. Results: Severe thermal injury in addition to distal ear-hole wounds induced marked local and systemic inflammatory responses in the lungs and significantly augmented the expression of inflammatory mediators in the ear tissue. By day 14, 61% of the ear-hole wounds from thermally injured mice demonstrated extensive inflammation with marked inflammatory cell infiltration, extensive ulceration, and various level of necrosis to the point where a large percentage (38%) had to be euthanized early during the study due to extensive necrosis, inflammation and ear deformation. By day 35, ear-hole wounds in mice not subjected to thermal injury were completely closed, while the ear-hole wounds in thermally injured mice exhibited less inflammation and necrosis and only closed partially (62%). Thermal injury resulted in marked increases in serum levels of IL-6, TNFalpha, KC (CXCL1), and MIP-2alpha (CXCL2). Interestingly, attenuated early ear wound healing in the thermally injured mouse resulted in incomplete tissue regeneration in addition to a marked inflammatory response, as evidenced by the histological appearance of the wound and increased transcription of potent inflammatory mediators.

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Document Details

Document Type
Technical Report
Publication Date
Jan 01, 2010
Accession Number
ADA532942

Entities

People

  • Eric A. Elster
  • Khairul Anam
  • Mihret F Amare
  • Stephen R. Zins
  • Thomas A. Davis

Organizations

  • Naval Medical Research Center

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Biological Factors
  • Biomedical Research
  • Blood
  • Burns
  • Cells
  • Data Analysis
  • Gene Expression
  • Governments
  • Granulocytes
  • Immune System
  • Necrosis
  • Phagocytes
  • Polymerase Chain Reaction
  • Proteins
  • Regeneration (Physiology)
  • United States Government
  • Wound Healing

Fields of Study

  • Medicine

Readers

  • Immunology and Pathology
  • Trauma Surgery or Emergency Medicine.