[Skip to Content]
Sign In
Individual Sign In
Create an Account
Institutional Sign In
OpenAthens Shibboleth
[Skip to Content Landing]
Article
January 1990

Are the Catabolic Effects of Tumor Necrosis Factor Mediated by Glucocorticoids?

Author Affiliations

From the Departments of Surgery (Drs Mealy, van Lanschot, and Wilmore and Ms Rounds) and Medicine (Dr Robinson), Brigham and Woman's Hospital, Harvard Medical School, Boston, Mass.

Arch Surg. 1990;125(1):42-48. doi:10.1001/archsurg.1990.01410130044006
Abstract

• The effect of tumor necrosis factor (TNF) on the hypothalamic-adrenal stress response was determined by infusion of TNF, 0, 2×105, and 4× 105 U/kg per 24 hours, in parenterally fed male Wistar rats. Following infusions over 1 to 6 days, adrenal weight was increased with increasing dosage of TNF. Tumor necrosis factor at a dosage of 4× 105 U/kg per 24 hours increased the plasma corticotropin level over the same period. In a further series of experiments the metabolic effects of TNF were compared with the effects of corticosterone, the predominant glucocorticoid in the rat. In comparison with controls, rats given corticosterone (75 mg subcutaneously) or TNF (2× 105 U/kg per 24 hours) demonstrated decreased nitrogen balance and diminished carcass nitrogen content over a 6-day period. Tumor necrosis factor alone, however, induced a significant increase in liver nitrogen content and diminished jejunal mucosa DNA and protein levels in comparison with the control and corticosterone groups. Finally, adrenalectomized animals receiving basal corticosterone replacement were infused with TNF. Urinary nitrogen loss was significantly diminished in these animals compared with sham adrenalectomized controls, indicating that an intact adrenal stress response is necessary for the increased nitrogen loss following TNF infusion. Tumor necrosis factor may exert an important regulatory influence on the interorgan substrate flux that occurs during critical illness. The effects of TNF on skeletal muscle proteolysis can be simulated by adrenal glucocorticoid administration. The effects of this cytokine on visceral organs appear to be unique to TNF and cannot be reproduced by the administration of glucocorticoids alone.

(Arch Surg. 1990;125:42-48)

References
1.
Beisel W.  Metabolic response to infection . Ann Rev Med . 1975;26:9-20.Article
2.
Wilmore D. The Metabolic Management of the Critically Ill. New York, NY: Plenum Publishing Corp; 1977.
3.
Watters J, Bessey P, Dinarello C, Wolff S, Wilmore D.  Both inflammatory and endocrine mediators stimulate host responses to sepsis . Arch Surg . 1986;121:179-190.Article
4.
Tracey K, Fong Y, Hesse D, et al.  Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia . Nature . 1987;330:662-664.Article
5.
Beutler B, Milsark I, Cerami A.  Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin . Science . 1985;229:869-871.Article
6.
Beutler B, Cerami B.  Cachectin and tumour necrosis factor as two sides of the same biological coin . Nature . 1986;320:146-154.Article
7.
Moldawer L, Svaninger G, Gelin J, Lundholm K.  Interleukin-1 and tumor necrosis factor do not regulate protein balance in skeletal muscle . Am J Physiol . 1987;253:C766-C773.
8.
Goldberg A, Kettlehut I, Furuno K, Fagan J, Baracos V.  Activation of protein breakdown and prostaglandin E2 production in rat skeletal muscle in fever is signaled by a macrophage product distinct from interleukin-1 or other known monokines . J Clin Invest . 1988;81:1378-1383.Article
9.
Jacobs D, Evans D, Mealy K, O'Dwyer S, Smith R, Wilmore D.  Combined effects of glutamine and epidural growth factor on the rat intestine . Surgery . 1988;104:358-364.
10.
Peters J, Van Slyke D.  Total and non-protein nitrogen . In: Quantitative Clinical Chemistry. Baltimore, Md: Williams & Wilkins; 1932:516-538.
11.
Burton K.  A study of the conditions and mechanism of the diphenylamine reaction of the colorimetric estimation of deoxyribonucleic acid . Biochem J . 1956;62:315-322.
12.
Lowry O, Rosebrough N, Farr A, Randall R.  Protein measurement with the folin phenol method . JBiol Chem . 1951;193:265-275.
13.
Starnes H, Warren R, Jeevanandam M, et al.  Tumor necrosis factor in the acute metabolic response to tissue injury in man . J Clin Invest . 1988; 82:1321-1325.Article
14.
Warren R, Starnes F, Gabrilove J, Oettgen H, Brennan M.  The acute metabolic effects of tumor necrosis factor administration in humans . Arch Surg . 1987;122:1396-1400.Article
15.
Michie H, Sherman M, Spriggs D, Rounds J, Christie M, Wilmore D.  Chronic TNF infusion causes anorexia but not accelerated nitrogen loss . Ann Surg . 1989;209:19-24.Article
16.
Michie H, Spriggs D, Manogue K, et al.  Tumor necrosis factor and endotoxin induce similar metabolic responses in human beings . Surgery . 1988;104:280-286.
17.
Ryan W, Carver M.  Immediate and prolonged effects of hydrocortisone on the free amino acid of rat skeletal muscle . Proc Soc Exp Biol Med . 1963;114:816-819.Article
18.
Muhlbacher F, Kapadia C, Colpoys M, Smith R, Wilmore D.  Effects of glucocorticoids on glutamine metabolism in skeletal muscle . Am J Physiol . 1984;247:E75-E83.
19.
Bertini R, Bianchi M, Ghezzi P.  Adrenalectomy sensitizes mice to the lethal effects of interleukin-1 and tumor necrosis factor . J Exp Med . 1988;167:1708-1712.Article
20.
Fong Y, Moldawer L, Marano M, et al.  Cachectin/TNF or IL-1 alpha induces cachexia with redistribution of body proteins . Am J Physiol . 1989;256:R659-R665.
21.
Arturson G.  Pathophysiological aspects of the burn syndrome . Acta Chir Scand . 1961;274( (suppl) ):1-135.
22.
Baumann H, Onorato V, Gauldie J, Jahreis G.  Distinct sets of acute phase plasma proteins are stimulated by separate human hepatocyte-stimulating factors and monokines in rat hepatoma cells . J Biol Chem . 1987;262:9756-9768.
23.
Baumann H, Hill R, Sauder D, Jahreis G.  Regulation of major acute-phase plasma proteins by hepatocyte-stimulating factors of human squamous carcinoma cells . J Cell Biol . 1986;102:370-383.Article
24.
Gaudie J, Richards C, Harnish D, Lansdorp P, Baumann H.  Interferon β2/B-cell stimulating factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells . Proc Nati Acad Sci USA . 1987;84:7251-7255.Article
25.
Kohase M, Henriksen-DeStefano D, May L, Vilcek J, Sehgal P.  Induction of β2-interferon by tumor necrosis factor: a homeostatic mechanism in the control of cell proliferation . Cell . 1986;45:659-666.Article
26.
Tracey K, Beutler B, Lowry S, Merryweather J, Wolpe S, et al.  Shock and tissue injury induced by recombinant cachectin . Science . 1986;234:470-474.Article
27.
Carswell E, Old L, Kassel R, Green S, Fiore N, Williamson B.  An endotoxin induced serum factor that causes necrosis of tumors . Proc Natl Acad Sci USA . 1975;72:3666-3670.Article
28.
Carswell E, Green S, Everson T, et al.  Effect of tumor necrosis factor on cultured human melanoma cells . Nature . 1975;258:731-732.Article
29.
Sugarman B, Aggarwal B, Hass P, Figari I, Palladino M Jr, Shepard H.  Recombinant human tumor necrosis factor alpha: effects on proliferation of normal and transformed cells in vitro . Science . 1985;230:943-945.Article
30.
Broxmeyer H, Williams D, Lu L, et al.  The suppressive influences of human tumor necrosis factors on bone marrow hematopoietic progenitor cells form normal donors and patients with leukemia: synergism of tumor necrosis factor and interferon-gamma . J Immunol . 1986;136:4487-4495.
31.
Roodman G.  Mechanisms of erythroid suppression in the anemia of chronic disease . Blood Cells . 1987;13:171-184.
32.
Sun X, Hsueh W.  Tumor necrosis factor (TNF)-induced bowel necrosis in rats: the role of platelet activating factor (PAF) . FASEB J . 1988;2:A414.
×