This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Feezor, R. J. Articles by Oberholzer, A. Search for Related Content PubMed PubMed Citation Articles by Feezor, R. J. Articles by Oberholzer, A.

 Previous Article  |  Next Article 

Infection and Immunity, October 2003, p. 5803-5813, Vol. 71, No. 10
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.10.5803-5813.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Molecular Characterization of the Acute Inflammatory Response to Infections with Gram-Negative versus Gram-Positive Bacteria

Department of Surgery,¹ Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida 32610,³ Department of Trauma and Reconstructive Surgery, Benjamin Franklin Medical Center, Berlin, Germany,² Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel,⁴ ICOS Inc., Bothell, Washington 98021,⁵ Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262⁶

Received 10 February 2003/ Returned for modification 14 April 2003/ Accepted 27 June 2003

Sepsis caused by gram-negative bacteria and that caused by gram-positive bacteria often manifest similar clinical features. We investigated plasma proinflammatory cytokine profiles in patients with sepsis due to gram-positive and gram-negative bacteria and studied the cytokine production and differential gene regulation of leukocytes stimulated ex vivo with Escherichia coli lipopolysaccharide or heat-killed Staphylococcus aureus. Concentrations of tumor necrosis factor alpha, interleukin 1 receptor antagonist (IL-1Ra), IL-8, IL-10, IL-18 binding protein, procalcitonin, and protein C in plasma did not differ between patients with sepsis due to gram-negative and gram-positive bacteria. However, plasma IL-1ß, IL-6, and IL-18 concentrations were significantly higher in patients with sepsis due to gram-positive bacteria. Ex vivo stimulation of whole blood with heat-killed S. aureus markedly increased IL-1ß and IL-18 levels more than E. coli lipopolysaccharide stimulation. Microarray analysis revealed at least 359 cross-validated probe sets (genes) significant at the P < 0.001 level whose expression discriminated among gram-negative-organism-stimulated, gram-positive-organism-stimulated, and unstimulated whole-blood leukocytes. The host inflammatory responses to gram-negative and gram-positive stimuli share some common response elements but also exhibit distinct patterns of cytokine appearance and leukocyte gene expression.

Editor: F. C. Fang

This article has been cited by other articles:

• Lukaszewski, R. A., Yates, A. M., Jackson, M. C., Swingler, K., Scherer, J. M., Simpson, A. J., Sadler, P., McQuillan, P., Titball, R. W., Brooks, T. J. G., Pearce, M. J. (2008). Presymptomatic Prediction of Sepsis in Intensive Care Unit Patients. CVI 15: 1089-1094 [Abstract] [Full Text]  
• Rydkina, E., Sahni, A., Silverman, D. J., Sahni, S. K. (2007). Comparative analysis of host-cell signalling mechanisms activated in response to infection with Rickettsia conorii and Rickettsia typhi. J Med Microbiol 56: 896-906 [Abstract] [Full Text]  
• Wiersinga, W. J., Dessing, M. C., Kager, P. A., Cheng, A. C., Limmathurotsakul, D., Day, N. P., Dondorp, A. M., van der Poll, T., Peacock, S. J. (2007). High-Throughput mRNA Profiling Characterizes the Expression of Inflammatory Molecules in Sepsis Caused by Burkholderia pseudomallei. Infect. Immun. 75: 3074-3079 [Abstract] [Full Text]  
• Elson, G., Dunn-Siegrist, I., Daubeuf, B., Pugin, J. (2007). Contribution of Toll-like receptors to the innate immune response to Gram-negative and Gram-positive bacteria. Blood 109: 1574-1583 [Abstract] [Full Text]  
• Talwar, S., Munson, P. J., Barb, J., Fiuza, C., Cintron, A. P., Logun, C., Tropea, M., Khan, S., Reda, D., Shelhamer, J. H., Danner, R. L., Suffredini, A. F. (2006). Gene expression profiles of peripheral blood leukocytes after endotoxin challenge in humans. Physiol. Genomics 25: 203-215 [Abstract] [Full Text]  
• Tavares, E., Maldonado, R., Ojeda, M. L., Minano, F. J. (2005). Circulating Inflammatory Mediators during Start of Fever in Differential Diagnosis of Gram-Negative and Gram-Positive Infections in Leukopenic Rats. CVI 12: 1085-1093 [Abstract] [Full Text]  
• Strassheim, D., Kim, J.-Y., Park, J.-S., Mitra, S., Abraham, E. (2005). Involvement of SHIP in TLR2-Induced Neutrophil Activation and Acute Lung Injury. J. Immunol. 174: 8064-8071 [Abstract] [Full Text]  
• Efron, P. A., Tsujimoto, H., Bahjat, F. R., Ungaro, R., Debernardis, J., Tannahill, C., Baker, H. V., Edwards, C. K., Moldawer, L. L. (2005). Differential maturation of murine bone-marrow derived dendritic cells with lipopolysaccharide and tumor necrosis factor-{alpha}. Innate Immunity 11: 145-160 [Abstract]  
• Moore, D. F., Li, H., Jeffries, N., Wright, V., Cooper, R. A. Jr, Elkahloun, A., Gelderman, M. P., Zudaire, E., Blevins, G., Yu, H., Goldin, E., Baird, A. E. (2005). Using Peripheral Blood Mononuclear Cells to Determine a Gene Expression Profile of Acute Ischemic Stroke: A Pilot Investigation. Circulation 111: 212-221 [Abstract] [Full Text]  
• Ji, Q., Zhang, L., Jia, H., Yang, J., Xu, J. (2004). Pentoxifylline Inhibits Endotoxin-Induced NF-kappa B Activation and Associated Production of Proinflammatory Cytokines. Annals of Clinical & Laboratory Science 34: 427-436 [Abstract] [Full Text]  
• Carrigan, S. D., Scott, G., Tabrizian, M. (2004). Toward Resolving the Challenges of Sepsis Diagnosis. Clin. Chem. 50: 1301-1314 [Abstract] [Full Text]  
• Netea, M. G., van der Graaf, C., Van der Meer, J. W. M., Kullberg, B. J. (2004). Toll-like receptors and the host defense against microbial pathogens: bringing specificity to the innate-immune system. J. Leukoc. Biol. 75: 749-755 [Abstract] [Full Text]