Abstract
BACKGROUND: Systemic inflammatory response syndrome (SIRS) is a mild inflammatory episode which, in a minority of patients, may deteriorate into septic shock. In the mouse, injection of bacteria or bacterial endotoxin induces systemic inflammation through the activation of blood monocytes, which leads to lethal shock. A number of intervention strategies have been shown to prevent progression to shock in mouse model systems. However, recent clinical trials of a number of these therapeutic strategies in patients have been uniformly disappointing. In contrast to the situation in the mouse models, there may be many different ways to initiate systemic inflammation in patients and not all of them need necessarily involve activation of blood monocytes. If there is no unifying mechanism behind the induction of systemic inflammation in patients and no common rules governing its development, then it is unlikely that generally applicable therapeutic strategies will be found that can prevent progression into shock. MATERIALS AND METHODS: We used differential display to compare gene expression patterns in monocytes of recent-admission multi-trauma patients with clinically diagnosed SIRS to the patterns in monocytes of healthy controls. RESULTS: Of seven differentially displayed bands that were recovered and sequenced, five were associated with SIRS and two were preferentially expressed in the monocytes of healthy controls. CONCLUSION: The data show that monocytes of SIRS patients are in an activation state that is different from that of monocytes from the healthy controls, that monocytes from many individual patients share similar patterns of differentially expressed sequences, and that by this criterion, the multi-trauma SIRS patients are a remarkably coherent group.
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- Bauer D., Müller H., Reich J., Riedel H., Ahrenkiel V., Warthoe P., Strauss M. Identification of differentially expressed mRNA species by an improved display technique (DDRT-PCR). Nucleic Acids Res. 1993 Sep 11;21(18):4272–4280. doi: 10.1093/nar/21.18.4272. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bone R. C., Fisher C. J., Jr, Clemmer T. P., Slotman G. J., Metz C. A., Balk R. A. Sepsis syndrome: a valid clinical entity. Methylprednisolone Severe Sepsis Study Group. Crit Care Med. 1989 May;17(5):389–393. [PubMed] [Google Scholar]
- Fisher C. J., Jr, Agosti J. M., Opal S. M., Lowry S. F., Balk R. A., Sadoff J. C., Abraham E., Schein R. M., Benjamin E. Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. The Soluble TNF Receptor Sepsis Study Group. N Engl J Med. 1996 Jun 27;334(26):1697–1702. doi: 10.1056/NEJM199606273342603. [DOI] [PubMed] [Google Scholar]
- Freudenberg M. A., Keppler D., Galanos C. Requirement for lipopolysaccharide-responsive macrophages in galactosamine-induced sensitization to endotoxin. Infect Immun. 1986 Mar;51(3):891–895. doi: 10.1128/iai.51.3.891-895.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Li P., Allen H., Banerjee S., Franklin S., Herzog L., Johnston C., McDowell J., Paskind M., Rodman L., Salfeld J. Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock. Cell. 1995 Feb 10;80(3):401–411. doi: 10.1016/0092-8674(95)90490-5. [DOI] [PubMed] [Google Scholar]
- Liang P., Pardee A. B. Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. Science. 1992 Aug 14;257(5072):967–971. doi: 10.1126/science.1354393. [DOI] [PubMed] [Google Scholar]
- McIntyre K. W., Stepan G. J., Kolinsky K. D., Benjamin W. R., Plocinski J. M., Kaffka K. L., Campen C. A., Chizzonite R. A., Kilian P. L. Inhibition of interleukin 1 (IL-1) binding and bioactivity in vitro and modulation of acute inflammation in vivo by IL-1 receptor antagonist and anti-IL-1 receptor monoclonal antibody. J Exp Med. 1991 Apr 1;173(4):931–939. doi: 10.1084/jem.173.4.931. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Opal S. M., Fisher C. J., Jr, Dhainaut J. F., Vincent J. L., Brase R., Lowry S. F., Sadoff J. C., Slotman G. J., Levy H., Balk R. A. Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. The Interleukin-1 Receptor Antagonist Sepsis Investigator Group. Crit Care Med. 1997 Jul;25(7):1115–1124. doi: 10.1097/00003246-199707000-00010. [DOI] [PubMed] [Google Scholar]
- Pittet D., Rangel-Frausto S., Li N., Tarara D., Costigan M., Rempe L., Jebson P., Wenzel R. P. Systemic inflammatory response syndrome, sepsis, severe sepsis and septic shock: incidence, morbidities and outcomes in surgical ICU patients. Intensive Care Med. 1995 Apr;21(4):302–309. doi: 10.1007/BF01705408. [DOI] [PubMed] [Google Scholar]
- Rogy M. A., Auffenberg T., Espat N. J., Philip R., Remick D., Wollenberg G. K., Copeland E. M., 3rd, Moldawer L. L. Human tumor necrosis factor receptor (p55) and interleukin 10 gene transfer in the mouse reduces mortality to lethal endotoxemia and also attenuates local inflammatory responses. J Exp Med. 1995 Jun 1;181(6):2289–2293. doi: 10.1084/jem.181.6.2289. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Uberla K., Platzer C., Diamantstein T., Blankenstein T. Generation of competitor DNA fragments for quantitative PCR. PCR Methods Appl. 1991 Nov;1(2):136–139. doi: 10.1101/gr.1.2.136. [DOI] [PubMed] [Google Scholar]
- Welford S. M., Gregg J., Chen E., Garrison D., Sorensen P. H., Denny C. T., Nelson S. F. Detection of differentially expressed genes in primary tumor tissues using representational differences analysis coupled to microarray hybridization. Nucleic Acids Res. 1998 Jun 15;26(12):3059–3065. doi: 10.1093/nar/26.12.3059. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van Rhenen D. J., Jalink W., Huijgens P. C. Esterase staining in monocytes. J Clin Pathol. 1983 Feb;36(2):236–237. doi: 10.1136/jcp.36.2.236. [DOI] [PMC free article] [PubMed] [Google Scholar]