AJP - Endocrinology and Metabolism, Vol 261, Issue 4 E457-E465, Copyright © 1991 by American Physiological Society

ARTICLES

Tumor necrosis factor mimics the metabolic response to acute infection in healthy humans

T. Van der Poll, J. A. Romijn, E. Endert, J. J. Borm, H. R. Buller and H. P. Sauerwein
Department of Internal Medicine, University of Amsterdam, The Netherlands.

To evaluate the role of tumor necrosis factor (TNF) in the initiation of the metabolic response to acute infection, we performed a crossover saline-controlled study in six healthy postabsorptive men, investigating the metabolic effects of a bolus intravenous injection of recombinant human TNF (50 micrograms/m2). TNF induced a transient stress hormone response, associated with an early and sustained rise in plasma glucose concentrations (percentage increase at 2 h 23 +/- 7; P less than 0.05). Glucose turnover, measured 7.5 h postinjection, was 10 +/- 3% higher after TNF administration (P less than 0.05). Plasma free fatty acids (FFA) and glycerol concentrations increased transiently after TNF injection, peaking after 4 h (percentage increase 363 +/- 83 and 67 +/- 14, respectively; both P less than 0.05). FFA turnover, determined 6.5 h postinjection, increased in five subjects to a variable extent (percentage increase 126 +/- 55; P less than 0.05). Finally, resting energy expenditure showed a transient rise after TNF injection (34 +/- 2% at 4 h; P less than 0.05). We conclude that intravenous TNF reproduces many of the metabolic changes observed in septicemia, suggesting that TNF may be an initiating factor in the development of the metabolic response to acute infection.

This article has been cited by other articles:

				R. Krogh-Madsen, K. Moller, F. Dela, G. Kronborg, S. Jauffred, and B. K. Pedersen Effect of hyperglycemia and hyperinsulinemia on the response of IL-6, TNF-{alpha}, and FFAs to low-dose endotoxemia in humans Am J Physiol Endocrinol Metab, May 1, 2004; 286(5): E766 - E772. [Abstract] [Full Text] [PDF]

				J. de Metz, J. A. Romijn, E. Endert, M. T. Ackermans, G. J. Weverling, O. R. Busch, L. Th. de Wit, D. J. Gouma, I. J. M. t. Berge, and H. P. Sauerwein Interferon-{gamma} increases monocyte HLA-DR expression without effects on glucose and fat metabolism in postoperative patients J Appl Physiol, February 1, 2004; 96(2): 597 - 603. [Abstract] [Full Text] [PDF]

				J. A. Johnson, J. B. Albu, E. S. Engelson, S. K. Fried, Y. Inada, G. Ionescu, and D. P. Kotler Increased systemic and adipose tissue cytokines in patients with HIV-associated lipodystrophy Am J Physiol Endocrinol Metab, February 1, 2004; 286(2): E261 - E271. [Abstract] [Full Text] [PDF]

				H. H. Zhang, M. Halbleib, F. Ahmad, V. C. Manganiello, and A. S. Greenberg Tumor Necrosis Factor-{alpha} Stimulates Lipolysis in Differentiated Human Adipocytes Through Activation of Extracellular Signal-Related Kinase and Elevation of Intracellular cAMP Diabetes, October 1, 2002; 51(10): 2929 - 2935. [Abstract] [Full Text] [PDF]

				H. S. Moeniralam, F. Sprangers, E. Endert, M. T. Ackermans, J. J. B. Van Lanschot, H. P. Sauerwein, and J. A. Romijn Role of nitric oxide in the regulation of glucose kinetics in response to endotoxin in dogs J Appl Physiol, July 1, 2001; 91(1): 130 - 136. [Abstract] [Full Text] [PDF]

				D. Le Roith and Y. Zick Recent Advances in Our Understanding of Insulin Action and Insulin Resistance Diabetes Care, March 1, 2001; 24(3): 588 - 597. [Abstract] [Full Text]

				M. Blüher, J. Kratzsch, and R. Paschke Plasma Levels of Tumor Necrosis Factor-{alpha}, Angiotensin II, Growth Hormone, and IGF-I Are Not Elevated in Insulin-Resistant Obese Individuals With Impaired Glucose Tolerance Diabetes Care, February 1, 2001; 24(2): 328 - 334. [Abstract] [Full Text]

				J. de Metz, F. Sprangers, E. Endert, M. T. Ackermans, I. J. M. ten Berge, H. P. Sauerwein, and J. A. Romijn Interferon-gamma has immunomodulatory effects with minor endocrine and metabolic effects in humans J Appl Physiol, February 1, 1999; 86(2): 517 - 522. [Abstract] [Full Text] [PDF]

				M. Ryden, A. Dicker, V. van Harmelen, H. Hauner, M. Brunnberg, L. Perbeck, F. Lonnqvist, and P. Arner Mapping of Early Signaling Events in Tumor Necrosis Factor-alpha -mediated Lipolysis in Human Fat Cells J. Biol. Chem., January 4, 2002; 277(2): 1085 - 1091. [Abstract] [Full Text] [PDF]

				O. N. Ozes, H. Akca, L. D. Mayo, J. A. Gustin, T. Maehama, J. E. Dixon, and D. B. Donner A phosphatidylinositol 3-kinase/Akt/mTOR pathway mediates and PTEN antagonizes tumor necrosis factor inhibition of insulin signaling through insulin receptor substrate-1 PNAS, April 10, 2001; 98(8): 4640 - 4645. [Abstract] [Full Text] [PDF]