T van der Poll, CV Keogh, WA Buurman and SF Lowry
Cornell University Medical College, Department of Surgery, New York, New York 10021, USA.

Streptococcus pneumoniae is the most frequent cause of community- acquired pneumonia. We sought to determine the role of tumor necrosis factor-alpha (TNF) in the pathogenesis of pneumococcal pneumonia. Induction of pneumonia in C57B1/6 mice by intranasal inoculation with 10(6) colony-forming units (cfu) S. pneumoniae resulted in a sustained increase in TNF activity in lung homogenates reaching a plateau between 12 and 72 h (72 h: 185.49 +/- 54.41 ng/g), while plasma TNF activity remained low or undetectable. Treatment with a neutralizing anti-TNF monoclonal antibody 2 h before inoculation strongly reduced lung TNF activity, but only modestly diminished lung interleukin (IL)-1beta levels, and did not significantly influence lung IL-6, IL-10, and interferon-gamma concentrations. Anti-TNF-treated mice had fourfold more S. pneumoniae cfu isolated from lungs than control mice 40 h after inoculation (p < 0.05), although lung myeloperoxidase activities were similar in both treatment groups. Anti-TNF-treated mice died significantly earlier from pneumococcal pneumonia than control mice (p < 0.05). Endogenously produced TNF is important for host defense during pneumococcal pneumonia.

This article has been cited by other articles:

				D. Kafka, E. Ling, G. Feldman, D. Benharroch, E. Voronov, N. Givon-Lavi, Y. Iwakura, R. Dagan, R. N. Apte, and Y. Mizrachi-Nebenzahl Contribution of IL-1 to resistance to Streptococcus pneumoniae infection Int. Immunol., September 1, 2008; 20(9): 1139 - 1146. [Abstract] [Full Text] [PDF]

				M. C. Dessing, K. F. van der Sluijs, S. Florquin, S. Akira, and T. van der Poll Toll-Like Receptor 2 Does Not Contribute to Host Response during Postinfluenza Pneumococcal Pneumonia Am. J. Respir. Cell Mol. Biol., May 1, 2007; 36(5): 609 - 614. [Abstract] [Full Text] [PDF]

				L. J. Quinton, M. R. Jones, B. T. Simms, M. S. Kogan, B. E. Robson, S. J. Skerrett, and J. P. Mizgerd Functions and Regulation of NF-{kappa}B RelA during Pneumococcal Pneumonia J. Immunol., February 1, 2007; 178(3): 1896 - 1903. [Abstract] [Full Text] [PDF]

				M. C. Dessing, A. F. de Vos, S. Florquin, and T. van der Poll Monocyte Chemoattractant Protein 1 Does Not Contribute to Protective Immunity against Pneumococcal Pneumonia Infect. Immun., December 1, 2006; 74(12): 7021 - 7023. [Abstract] [Full Text] [PDF]

				H. M. Marriott, P. G. Hellewell, S. S. Cross, P. G. Ince, M. K. B. Whyte, and D. H. Dockrell Decreased Alveolar Macrophage Apoptosis Is Associated with Increased Pulmonary Inflammation in a Murine Model of Pneumococcal Pneumonia J. Immunol., November 1, 2006; 177(9): 6480 - 6488. [Abstract] [Full Text] [PDF]

				J. F. P. Berbee, C. C. van der Hoogt, R. Kleemann, E. F. Schippers, R. L. Kitchens, J. T. van Dissel, I. A. J. M. Bakker-Woudenberg, L. M. Havekes, and P. C. N. Rensen Apolipoprotein CI stimulates the response to lipopolysaccharide and reduces mortality in Gram-negative sepsis FASEB J, October 1, 2006; 20(12): 2162 - 2164. [Abstract] [Full Text] [PDF]

				S. Yende, E. I. Tuomanen, R. Wunderink, A. Kanaya, A. B. Newman, T. Harris, N. de Rekeneire, S. B. Kritchevsky, and for the Health ABC Study Preinfection Systemic Inflammatory Markers and Risk of Hospitalization Due to Pneumonia Am. J. Respir. Crit. Care Med., December 1, 2005; 172(11): 1440 - 1446. [Abstract] [Full Text] [PDF]

				M. Tanabe, T. Matsumoto, K. Shibuya, K. Tateda, S. Miyazaki, A. Nakane, Y. Iwakura, and K. Yamaguchi Compensatory response of IL-1 gene knockout mice after pulmonary infection with Klebsiella pneumoniae J. Med. Microbiol., January 1, 2005; 54(1): 7 - 13. [Abstract] [Full Text] [PDF]

				J. P. Mizgerd, M. M. Lupa, J. Hjoberg, J. C. Vallone, H. B. Warren, J. P. Butler, and E. S. Silverman Roles for early response cytokines during Escherichia coli pneumonia revealed by mice with combined deficiencies of all signaling receptors for TNF and IL-1 Am J Physiol Lung Cell Mol Physiol, June 1, 2004; 286(6): L1302 - L1310. [Abstract] [Full Text] [PDF]

				A. H. van Kaam, R. A. Lachmann, E. Herting, A. De Jaegere, F. van Iwaarden, L. A. Noorduyn, J. H. Kok, J. J. Haitsma, and B. Lachmann Reducing Atelectasis Attenuates Bacterial Growth and Translocation in Experimental Pneumonia Am. J. Respir. Crit. Care Med., May 1, 2004; 169(9): 1046 - 1053. [Abstract] [Full Text] [PDF]

				S. Knapp, C. W. Wieland, C. van 't Veer, O. Takeuchi, S. Akira, S. Florquin, and T. van der Poll Toll-Like Receptor 2 Plays a Role in the Early Inflammatory Response to Murine Pneumococcal Pneumonia but Does Not Contribute to Antibacterial Defense J. Immunol., March 1, 2004; 172(5): 3132 - 3138. [Abstract] [Full Text] [PDF]

				J. P. Mizgerd Competing Benefits of Tumor Necrosis Factor-{alpha} for Bacteria and for Host Defense Am. J. Respir. Crit. Care Med., December 15, 2003; 168(12): 1410 - 1411. [Full Text] [PDF]

				J.-H. Lee, L. Del Sorbo, A. A. Khine, J. de Azavedo, D. E. Low, D. Bell, S. Uhlig, A. S. Slutsky, and H. Zhang Modulation of Bacterial Growth by Tumor Necrosis Factor-{alpha} In Vitro and In Vivo Am. J. Respir. Crit. Care Med., December 15, 2003; 168(12): 1462 - 1470. [Abstract] [Full Text] [PDF]

				T. A. Moore, M. L. Perry, A. G. Getsoian, C. L. Monteleon, A. L. Cogen, and T. J. Standiford Increased Mortality and Dysregulated Cytokine Production in Tumor Necrosis Factor Receptor 1-Deficient Mice following Systemic Klebsiella pneumoniae Infection Infect. Immun., September 1, 2003; 71(9): 4891 - 4900. [Abstract] [Full Text] [PDF]

				B. M. Schaaf, F. Boehmke, H. Esnaashari, U. Seitzer, H. Kothe, M. Maass, P. Zabel, and K. Dalhoff Pneumococcal Septic Shock Is Associated with the Interleukin-10-1082 Gene Promoter Polymorphism Am. J. Respir. Crit. Care Med., August 15, 2003; 168(4): 476 - 480. [Abstract] [Full Text] [PDF]

				M. J. Schultz, S. Knapp, S. Florquin, J. Pater, K. Takeda, S. Akira, and T. van der Poll Interleukin-18 Impairs the Pulmonary Host Response to Pseudomonas aeruginosa Infect. Immun., April 1, 2003; 71(4): 1630 - 1634. [Abstract] [Full Text]

				T. A. Moore, M. L. Perry, A. G. Getsoian, M. W. Newstead, and T. J. Standiford Divergent Role of Gamma Interferon in a Murine Model of Pulmonary versus Systemic Klebsiella pneumoniae Infection Infect. Immun., November 1, 2002; 70(11): 6310 - 6318. [Abstract] [Full Text] [PDF]

				A. R. Kerr, J. J. Irvine, J. J. Search, N. A. Gingles, A. Kadioglu, P. W. Andrew, W. L. McPheat, C. G. Booth, and Tim. J. Mitchell Role of Inflammatory Mediators in Resistance and Susceptibility to Pneumococcal Infection Infect. Immun., March 1, 2002; 70(3): 1547 - 1557. [Abstract] [Full Text] [PDF]

				F. N. Lauw, J. Branger, S. Florquin, P. Speelman, S. J. H. van Deventer, S. Akira, and T. van der Poll IL-18 Improves the Early Antimicrobial Host Response to Pneumococcal Pneumonia J. Immunol., January 1, 2002; 168(1): 372 - 378. [Abstract] [Full Text] [PDF]

				A. W. Rijneveld, S. Florquin, J. Branger, P. Speelman, S. J. H. Van Deventer, and T. van der Poll TNF-{alpha} Compensates for the Impaired Host Defense of IL-1 Type I Receptor-Deficient Mice During Pneumococcal Pneumonia J. Immunol., November 1, 2001; 167(9): 5240 - 5246. [Abstract] [Full Text] [PDF]

				M. J. SCHULTZ, A. W. RIJNEVELD, S. FLORQUIN, P. SPEELMAN, S. J. H. VAN DEVENTER, and T. VAN DER POLL Impairment of host defence by exotoxin A in Pseudomonas aeruginosa pneumonia in mice J. Med. Microbiol., September 1, 2001; 50(9): 822 - 827. [Abstract] [Full Text] [PDF]

				D. Le Roy, F. Di Padova, Y. Adachi, M. P. Glauser, T. Calandra, and D. Heumann Critical Role of Lipopolysaccharide-Binding Protein and CD14 in Immune Responses against Gram-Negative Bacteria J. Immunol., September 1, 2001; 167(5): 2759 - 2765. [Abstract] [Full Text] [PDF]

				M. E. Sewnath, D. P. Olszyna, R. Birjmohun, F. J. W. ten Kate, D. J. Gouma, and T. van der Poll IL-10-Deficient Mice Demonstrate Multiple Organ Failure and Increased Mortality During Escherichia coli Peritonitis Despite an Accelerated Bacterial Clearance J. Immunol., May 15, 2001; 166(10): 6323 - 6331. [Abstract] [Full Text] [PDF]

				M. J. Schultz, J. Wijnholds, M. P. Peppelenbosch, M. J. B. M. Vervoordeldonk, P. Speelman, S. J. H. van Deventer, P. Borst, and T. van der Poll Mice Lacking the Multidrug Resistance Protein 1 Are Resistant to Streptococcus pneumoniae-Induced Pneumonia J. Immunol., March 15, 2001; 166(6): 4059 - 4064. [Abstract] [Full Text] [PDF]

				S. Nelson Novel Nonantibiotic Therapies for Pneumonia : Cytokines and Host Defense Chest, February 1, 2001; 119(2_suppl): 419S - 425S. [Abstract] [Full Text] [PDF]

				O. GIRAUD, P.-F. SEINCE, C. ROLLAND, V. LEÇON-MALAS, J.-M. DESMONTS, M. AUBIER, and M. DEHOUX Halothane Reduces the Early Lipopolysaccharide-induced Lung Inflammation in Mechanically Ventilated Rats Am. J. Respir. Crit. Care Med., December 1, 2000; 162(6): 2278 - 2286. [Abstract] [Full Text]

				L. V. Kendall, L. K. Riley, R. R. Hook Jr., C. L. Besch-Williford, and C. L. Franklin Antibody and Cytokine Responses to the Cilium-Associated Respiratory Bacillus in BALB/c and C57BL/6 Mice Infect. Immun., September 1, 2000; 68(9): 4961 - 4967. [Abstract] [Full Text] [PDF]

				M. J. Schultz, P. Speelman, C. E. Hack, W. A. Buurman, S. J. H. van Deventer, and T. van der Poll Intravenous infusion of erythromycin inhibits CXC chemokine production, but augments neutrophil degranulation in whole blood stimulated with Streptococcus pneumoniae J. Antimicrob. Chemother., August 1, 2000; 46(2): 235 - 240. [Abstract] [Full Text] [PDF]

				J. P. Mizgerd, J. J. Peschon, and C. M. Doerschuk Roles of Tumor Necrosis Factor Receptor Signaling during Murine Escherichia coli Pneumonia Am. J. Respir. Cell Mol. Biol., January 1, 2000; 22(1): 85 - 91. [Abstract] [Full Text]

				D. A. STOLTZ, S. NELSON, J. K. KOLLS, P. ZHANG, R. P. BOHM Jr., M. MURPHEY-CORB, and G. J. BAGBY In Vitro Ethanol Suppresses Alveolar Macrophage TNF-alpha during Simian Immunodeficiency Virus Infection Am. J. Respir. Crit. Care Med., January 1, 2000; 161(1): 135 - 140. [Abstract] [Full Text]

				J. LoCicero III, X. Xu, and L. Zhang Heat shock protein suppresses the senescent lung cytokine response to acute endotoxemia Ann. Thorac. Surg., October 1, 1999; 68(4): 1150 - 1153. [Abstract] [Full Text] [PDF]

				J R Catterall Lung infections bullet 5: Streptococcus pneumoniae Thorax, October 1, 1999; 54(10): 929 - 937. [Full Text]

				S. Videla, A. García-Lafuente, M. Antolín, J. Vilaseca, F. Guarner, E. Crespo, G. González, A. Salas, and J. R. Malagelada Antitumor Necrosis Factor Therapy in Rat Chronic Granulomatous Colitis: Critical Dose-Timing Effects on Outcome J. Pharmacol. Exp. Ther., December 1, 1998; 287(3): 854 - 859. [Abstract] [Full Text]

				Y. Bergeron, N. Ouellet, A.-M. Deslauriers, M. Simard, M. Olivier, and M. G. Bergeron Reduction by Cefodizime of the Pulmonary Inflammatory Response Induced by Heat-Killed Streptococcus pneumoniae in Mice Antimicrob. Agents Chemother., October 1, 1998; 42(10): 2527 - 2533. [Abstract] [Full Text]

				M. J. Schultz, P. Speelman, S. Zaat, S. J. H. van Deventer, and T. van der Poll Erythromycin Inhibits Tumor Necrosis Factor Alpha and Interleukin 6 Production Induced by Heat-Killed Streptococcus pneumoniae in Whole Blood Antimicrob. Agents Chemother., July 1, 1998; 42(7): 1605 - 1609. [Abstract] [Full Text]

				Y. Bergeron, N. Ouellet, A.-M. Deslauriers, M. Simard, M. Olivier, and M. G. Bergeron Cytokine Kinetics and Other Host Factors in Response to Pneumococcal Pulmonary Infection in Mice Infect. Immun., March 1, 1998; 66(3): 912 - 922. [Abstract] [Full Text] [PDF]

				T. van der Poll, S. M. Coyle, M. Levi, P. M. Jansen, M. Dentener, K. Barbosa, W. A. Buurman, C. E. Hack, J. W. ten Cate, J. M. Agosti, et al. Effect of a Recombinant Dimeric Tumor Necrosis Factor Receptor on Inflammatory Responses to Intravenous Endotoxin in Normal Humans Blood, May 15, 1997; 89(10): 3727 - 3734. [Abstract] [Full Text] [PDF]

				M. J. Schultz, A. W. Rijneveld, S. Florquin, C. K. Edwards, C. A. Dinarello, and T. van der Poll Role of interleukin-1 in the pulmonary immune response during Pseudomonas aeruginosa pneumonia Am J Physiol Lung Cell Mol Physiol, February 1, 2002; 282(2): L285 - L290. [Abstract] [Full Text] [PDF]