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in the Development of Systemic Inflammatory Response and Organ Injury following Trauma Hemorrhage1Center for Surgical Research and Department of Surgery, University of Alabama, Birmingham, AL 35294
Although MIP-1
is an important chemokine in the recruitment of inflammatory cells, it remains unknown whether MIP-1
plays any role in the development of systemic inflammatory response following trauma-hemorrhage (T-H). C57BL/6J wild type (WT) and MIP-1
-deficient (KO) mice were used either as control, subjected to sham operation (cannulation or laparotomy only or cannulation plus laparotomy) or T-H (midline laparotomy, mean blood pressure 35 ± 5 mmHg for 90 min, followed by resuscitation) and sacrificed 2 h thereafter. A marked increase in serum
-glutathione transferase, TNF-
, IL-6, IL-10, MCP-1, and MIP-1
and Kupffer cell cytokine production was observed in WT T-H mice compared with shams or control. In addition lung and liver tissue edema and neutrophil infiltration (myeloperoxidase (MPO) content) was also increased following T-H in WT animals. These inflammatory markers were markedly attenuated in the MIP-1
KO mice following T-H. Furthermore, compared with 2 h, MPO activities at 24 and 48 h after T-H declined steadily in both WT and KO mice. However, normalization of MPO activities to sham levels within 24 h was seen in KO mice but not in WT mice. Thus, MIP-1
plays an important role in mediating the acute inflammatory response following T-H. In the absence of MIP-1
, acute inflammatory responses were attenuated; rapidly recovered and less remote organ injury was noted following T-H. Thus, interventions that reduce MIP-1
levels following T-H should be useful in decreasing the deleterious inflammatory consequence of trauma.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grant R01 GM37127.
2 Current address: Department of Trauma and Emergency Surgery and Department of Surgery, China Medical University Hospital, China Medical University, Taichung, Taiwan.
3 Current address: Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
4 Address correspondence and reprint requests to Dr. Irshad H. Chaudry, Center for Surgical Research, University of Alabama, 1670 University Boulevard, G094 Volker Hall, Birmingham, AL 35294. E-mail address: Irshad.Chaudry{at}ccc.uab.edu
5 Abbreviations used in this paper: T-H, trauma-hemorrhage; KO, knock out; WT, wild type; MPO, myeloperoxidase;
-GST,
-glutathione transferase; CLP, cecal ligation and puncture.
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