Induction of early inflammatory gene expression in a murine model of nonresuscitated, fixed-volume hemorrhage

• Published in: Shock (Augusta, Ga.) Ga.), 2002-04, Vol.17 (4), p.322-328
• Main Authors: RAJNIK, Michael, SALKOWSKI, Cindy A, THOMAS, Karen E, LI, Ying-Yue, ROLLWAGEN, Florence M, VOGELT, Stefanie N
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Base Sequence; Biological and medical sciences; Cyclooxygenase 2; Cytokines - genetics; Disease Models, Animal; DNA, Complementary - genetics; Drosophila Proteins; Emergency and intensive cardiocirculatory care. Cardiogenic shock. Coronary intensive care; Female; Gene Expression; Hemorrhage - complications; Hemorrhage - genetics; Inflammation - etiology; Inflammation - genetics; Intensive care medicine; Isoenzymes - genetics; Medical sciences; Membrane Glycoproteins - genetics; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase Type II; Prostaglandin-Endoperoxide Synthases - genetics; Receptors, Cell Surface - genetics; Time Factors; Toll-Like Receptor 2; Toll-Like Receptors
• ISSN: 1073-2322; 1540-0514
• DOI: 10.1097/00024382-200204000-00015

The etiology of many end-organ problems associated with hemorrhage has been attributed to the inflammatory response to hemorrhage. In a murine model of nonresuscitated, fixed-volume hemorrhage, we sought to elucidate the role that hemorrhagic insult alone plays in the generation of the early inflammatory cascade. Differences could be appreciated as early as 1 h post-hemorrhage, with consistent differences detected by 3 h in all of the major cytokine genes studied. Significant upregulation of IL-1beta , IL-6, TNF-alpha, and IL-10 mRNA expression was observed in both the liver and lung samples of mice subjected to fixed-volume hemorrhage when compared with sham-hemorrhaged mice. The cyclooxygenase-2 (COX-2) and inducible nitric oxide synthetase (iNOS) genes also were upregulated in the livers and lungs of hemorrhaged mice. Finally, expression of the genes that encode the Toll-like receptors (TLR)-2 and -4 was increased by hemorrhage. Taken collectively, these data demonstrate that the initial inflammatory cascade associated with hemorrhage occurs within hours after the initial hemorrhagic event, and can be associated with significant modulation of expression of key pro- and anti-inflammatory cytokine, enzyme, and TLR genes, suggesting that these may be possible new therapeutic targets.