Interleukin (IL)-6 gene expression in the central nervous system is necessary for fever response to lipopolysaccharide or IL-1 beta: a study on IL-6-deficient mice

doi:10.1084/jem.183.1.311

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Interleukin (IL)-6 gene expression in the central nervous system is necessary for fever response to lipopolysaccharide or IL-1 beta: a study on IL-6-deficient mice

Z Chai, S Gatti, C Toniatti, V Poli and T Bartfai
Department of Neurochemistry and Neurotoxicology, Arrhenius Laboratories for Natural Sciences, Stockholm University, Sweden.

Interleukin (IL)-6, IL-1 beta, and tumor necrosis factor alpha (TNF- alpha) are considered to act as endogenous pyrogens. Because of the complex pattern of cross-inductions between these cytokines, the relative role of the central and peripheral production of these cytokines in eliciting the fever response has not yet been clarified. The purpose of this study was to determine the role of IL-6 in the fever response by making use of mice carrying a null mutation in the IL- 6 gene. The intraperitoneal injections of lipopolysaccharide (LPS) (50 micrograms/kg) and recombinant murine (rm) IL-1 beta (10 micrograms/kg), respectively, failed to evoke fever response in IL-6- deficient mice, whereas the same doses of LPS and rmIL-1 beta caused fever response in wild-type mice. The fever response could be induced in the IL-6-deficient mice by intracerebroventricular injection of recombinant human (rh) IL-6 (500 ng/mouse), whereas intracerebroventricular injection of rmIL-1 beta (100 ng/mouse) failed to produce fever response in the IL-6-deficient mice. These results suggest that central IL-6 is a necessary component of the fever response to both endogenous (IL-1 beta) and exogenous (LPS) pyrogens in mice and that IL-6 acts downstream from both peripheral and central IL- 1 beta.
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Chida, D., Osaka, T., Hashimoto, O., Iwakura, Y. (2006). Combined interleukin-6 and interleukin-1 deficiency causes obesity in young mice.. Diabetes 55: 971-977 [Abstract] [Full Text]
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Rudaya, A. Y., Steiner, A. A., Robbins, J. R., Dragic, A. S., Romanovsky, A. A. (2005). Thermoregulatory responses to lipopolysaccharide in the mouse: dependence on the dose and ambient temperature. Am. J. Physiol. Regul. Integr. Comp. Physiol. 289: R1244-R1252 [Abstract] [Full Text]
Remick, D. G., Bolgos, G., Copeland, S., Siddiqui, J. (2005). Role of Interleukin-6 in Mortality from and Physiologic Response to Sepsis. Infect. Immun. 73: 2751-2757 [Abstract] [Full Text]
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Turrin, N. P., Rivest, S. (2004). Unraveling the Molecular Details Involved in the Intimate Link between the Immune and Neuroendocrine Systems. Exp. Biol. Med. 229: 996-1006 [Abstract] [Full Text]
Kagiwada, K., Chida, D., Sakatani, T., Asano, M., Nambu, A., Kakuta, S., Iwakura, Y. (2004). Interleukin (IL)-6, But Not IL-1, Induction in the Brain Downstream of Cyclooxygenase-2 Is Essential for the Induction of Febrile Response against Peripheral IL-1{alpha}. Endocrinology 145: 5044-5048 [Abstract] [Full Text]
Dinarello, C. A. (2004). Review: Infection, fever, and exogenous and endogenous pyrogens: some concepts have changed. Innate Immunity 10: 201-222 [Abstract]
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Zhang, J., Rivest, S. (2003). Is Survival Possible Without Arachidonate Metabolites in the Brain During Systemic Infection?. Physiology 18: 137-142 [Abstract] [Full Text]
Mouihate, A., Pittman, Q. J. (2003). Neuroimmune Response to Endogenous and Exogenous Pyrogens Is Differently Modulated by Sex Steroids. Endocrinology 144: 2454-2460 [Abstract] [Full Text]
Leon, L. R. (2002). Molecular Biology of Thermoregulation: Invited Review: Cytokine regulation of fever: studies using gene knockout mice. J. Appl. Physiol. 92: 2648-2655 [Abstract] [Full Text]
Harre, E.-M., Roth, J., Pehl, U., Kueth, M., Gerstberger, R., Hubschle, T. (2002). Molecular Biology of Thermoregulation: Selected Contribution: Role of IL-6 in LPS-induced nuclear STAT3 translocation in sensory circumventricular organs during fever in rats. J. Appl. Physiol. 92: 2657-2666 [Abstract] [Full Text]
Nakagawa, Y., Maeda, H., Murai, T. (2002). Evaluation of the In Vitro Pyrogen Test System Based on Proinflammatory Cytokine Release from Human Monocytes: Comparison with a Human Whole Blood Culture Test System and with the Rabbit Pyrogen Test. CVI 9: 588-597 [Abstract] [Full Text]
Tesfaigzi, Y., Rudolph, K., Fischer, M. J., Conn, C. A. (2001). Bcl-2 mediates sex-specific differences in recovery of mice from LPS-induced signs of sickness independent of IL-6. J. Appl. Physiol. 91: 2182-2189 [Abstract] [Full Text]
Ladenheim, B., Krasnova, I. N., Deng, X., Oyler, J. M., Polettini, A., Moran, T. H., Huestis, M. A., Cadet, J. L. (2001). Methamphetamine-Induced Neurotoxicity Is Attenuated in Transgenic Mice with a Null Mutation for Interleukin-6. Mol. Pharmacol. 58: 1247-1256 [Abstract] [Full Text]
Dokladny, K., Kozak, A., Wachulec, M., Wallen, E. S., Menache, M. G., Kozak, W., Kluger, M. J., Moseley, P. L. (2001). Effect of heat stress on LPS-induced febrile response in D-galactosamine-sensitized rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 280: R338-R344 [Abstract] [Full Text]
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Sallmann, S., Juttler, E., Prinz, S., Petersen, N., Knopf, U., Weiser, T., Schwaninger, M. (2000). Induction of Interleukin-6 by Depolarization of Neurons. J. Neurosci. 20: 8637-8642 [Abstract] [Full Text]
Rivest, S., Lacroix, S., Vallières, L., Nadeau, S., Zhang, J., Laflamme, N. (2000). How the Blood Talks to the Brain Parenchyma and the Paraventricular Nucleus of the Hypothalamus During Systemic Inflammatory and Infectious Stimuli. Exp. Biol. Med. 223: 22-38 [Abstract] [Full Text]
Vallières, L., Rivest, S. (1999). Interleukin-6 Is a Needed Proinflammatory Cytokine in the Prolonged Neural Activity and Transcriptional Activation of Corticotropin-Releasing Factor during Endotoxemia. Endocrinology 140: 3890-3903 [Abstract] [Full Text]
Murphy, P. G., Borthwick, L. S., Johnston, R. S., Kuchel, G., Richardson, P. M. (1999). Nature of the Retrograde Signal from Injured Nerves that Induces Interleukin-6 mRNA in Neurons. J. Neurosci. 19: 3791-3800 [Abstract] [Full Text]
Gadient, R. A., Patterson, P. H. (1999). Leukemia Inhibitory Factor, Interleukin 6, and Other Cytokines Using the GP130 Transducing Receptor: Roles in Inflammation and Injury. Stem Cells 17: 127-137 [Abstract] [Full Text]
Myokai, F., Takashiba, S., Lebo, R., Amar, S. (1999). A novel lipopolysaccharide-induced transcription factor regulating tumor necrosis factor alpha �gene expression: Molecular cloning, sequencing, characterization, and chromosomal assignment. Proc. Natl. Acad. Sci. USA 96: 4518-4523 [Abstract] [Full Text]
Lundkvist, J., Sundgren-Andersson, A. K., Tingsborg, S., Ostlund, P., Engfors, C., Alheim, K., Bartfai, T., Iverfeldt, K., Schultzberg, M. (1999). Acute-phase responses in transgenic mice with CNS overexpression of IL-1 receptor antagonist. Am. J. Physiol. Regul. Integr. Comp. Physiol. 276: R644-R651 [Abstract] [Full Text]
Lenczowski, M. J.�P., Bluthe, R.-M., Roth, J., Rees, G. S., Rushforth, D. A., van Dam, A.-M., Tilders, F. J.�H., Dantzer, R., Rothwell, N. J., Luheshi, G. N. (1999). Central administration of rat IL-6 induces HPA activation and fever but not sickness behavior in rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 276: R652-R658 [Abstract] [Full Text]
Leon, L. R., Kozak, W., Rudolph, K., Kluger, M. J. (1999). An antipyretic role for interleukin-10 in LPS fever in mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 276: R81-R89 [Abstract] [Full Text]
Sundgren-Andersson, A. K., Ostlund, P., Bartfai, T. (1998). IL-6 is essential in TNF-alpha -induced fever. Am. J. Physiol. Regul. Integr. Comp. Physiol. 275: R2028-R2034 [Abstract] [Full Text]
Betz, U. A.K., Bloch, W., van den Broek, M., Yoshida, K., Taga, T., Kishimoto, T., Addicks, K., Rajewsky, K., Muller, W. (1998). Postnatally Induced Inactivation of gp130 in Mice Results in Neurological, Cardiac, Hematopoietic, Immunological, Hepatic, and Pulmonary Defects. J. Exp. Med. 188: 1955-1965 [Abstract] [Full Text]
KOZAK, W., KLUGER, M. J., SOSZYNSKI, D., CONN, C. A., RUDOLPH, K., LEON, L. R., ZHENG, H. (1998). IL-6 and IL-1{beta} in Fever: Studies Using Cytokine-Deficient (Knockout) Mice. Ann. N. Y. Acad. Sci. 856: 33-47 [Abstract] [Full Text]
ZETTERSTROM, M., SUNDGREN-ANDERSSON, A. K., OSTLUND, P., BARTFAI, T. (1998). Delineation of the Proinflammatory Cytokine Cascade in Fever Induction. Ann. N. Y. Acad. Sci. 856: 48-52 [Abstract] [Full Text]
LUHESHI, G. N. (1998). Cytokines and Fever: Mechanisms and Sites of Action. Ann. N. Y. Acad. Sci. 856: 83-89 [Abstract] [Full Text]
Leon, L. R., White, A. A., Kluger, M. J. (1998). Role of IL-6 and TNF in thermoregulation and survival during sepsis in mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 275: R269-R277 [Abstract] [Full Text]
Horai, R., Asano, M., Sudo, K., Kanuka, H., Suzuki, M., Nishihara, M., Takahashi, M., Iwakura, Y. (1998). Production of Mice Deficient in Genes for Interleukin (IL)-1alpha , IL-1beta , IL-1alpha /beta , and IL-1 Receptor Antagonist Shows that IL-1beta Is Crucial in Turpentine-induced Fever Development and Glucocorticoid Secretion. J. Exp. Med. 187: 1463-1475 [Abstract] [Full Text]
Marz, P., Cheng, J.-G., Gadient, R. A., Patterson, P. H., Stoyan, T., Otten, U., Rose-John, S. (1998). Sympathetic neurons can produce and respond to interleukin 6. Proc. Natl. Acad. Sci. USA 95: 3251-3256 [Abstract] [Full Text]
Perry, L. L., Feilzer, K., Caldwell, H. D. (1998). Neither Interleukin-6 nor Inducible Nitric Oxide Synthase Is Required for Clearance of Chlamydia trachomatis from the Murine Genital Tract Epithelium. Infect. Immun. 66: 1265-1269 [Abstract] [Full Text]
Alonzi, T., Fattori, E., Lazzaro, D., Costa, P., Probert, L., Kollias, G., De Benedetti, F., Poli, V., Ciliberto, G. (1998). Interleukin 6�Is Required for the Development of Collagen-induced Arthritis. J. Exp. Med. 187: 461-468 [Abstract] [Full Text]
Faggioni, R., Fantuzzi, G., Fuller, J., Dinarello, C. A., Feingold, K. R., Grunfeld, C. (1998). IL-1beta mediates leptin induction during inflammation. Am. J. Physiol. Regul. Integr. Comp. Physiol. 274: R204-R208 [Abstract] [Full Text]
Raber, J., O'Shea, R. D., Bloom, F. E., Campbell, I. L. (1997). Modulation of Hypothalamic-Pituitary-Adrenal Function by Transgenic Expression of Interleukin-6 in the CNS of Mice. J. Neurosci. 17: 9473-9480 [Abstract] [Full Text]
Philippe, L., Gegout-Pottie, P., Guingamp, C., Bordji, K., Terlain, B., Netter, P., Gillet, P. (1997). Relations between functional, inflammatory, and degenerative parameters during adjuvant arthritis in rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 273: R1550-R1556 [Abstract] [Full Text]
Kiani, A., Tschiersch, A., Gaboriau, E., Otto, F., Seiz, A., Knopf, H.-P., Stutz, P., Farber, L., Haus, U., Galanos, C., Mertelsmann, R., Engelhardt, R. (1997). Downregulation of the Proinflammatory Cytokine Response to Endotoxin by Pretreatment With the Nontoxic Lipid A Analog SDZ MRL 953�in Cancer Patients. Blood 90: 1673-1683 [Abstract] [Full Text]
Alheim, K., Chai, Z., Fantuzzi, G., Hasanvan, H., Malinowsky, D., Di Santo, E., Ghezzi, P., Dinarello, C. A., Bartfai, T. (1997). Hyperresponsive febrile reactions to interleukin (IL) 1alpha and IL-1beta , and altered brain cytokine mRNA and serum cytokine levels, in�IL-1beta -deficient�mice. Proc. Natl. Acad. Sci. USA 94: 2681-2686 [Abstract] [Full Text]