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Cysteine and Methionine Supplementation Modulate the Effect of Tumor Necrosis Factor on Protein Synthesis, Glutathione and Zinc Concentration of Liver and Lung in Rats Fed a Low Protein Diet^1,2,

Department of Human Nutrition, University of Southampton, Southampton SO16 7PX, U.K.

The synthesis of cysteine-rich compounds such as glutathione and metallothionein is an integral part of the response to cytokines. To examine the essentiality of an adequate supply of sulfur amino acids during a response to tumor necrosis factor (TNF) we fed rats a low protein (8% casein) diet supplemented with either cysteine and alanine, methionine and alanine, or alanine alone, or a normal protein (20% casein) diet for 8 d before injection with TNF or saline. Those animals injected with saline were pair-fed the intake of their TNF-injected counterparts for the 24 h after injection. In a second experiment, control groups fed the same diets but receiving no treatment were also examined to establish baseline values. Although few significant differences between the non-injected animals consuming food ad libitum were apparent, TNF injection and pair-feeding resulted in differences between the dietary groups. Supplementation of the low protein diet with either cysteine or methionine improved growth and increased liver and lung glutathione concentration, zinc concentration, protein concentration and protein synthesis compared with results for the alanine-supplemented group. Lung polymorphonuclear cells were proportionally elevated in the TNF-treated, alanine-supplemented group compared with the other dietary groups treated with TNF. The changes in protein synthesis and glutathione concentration of the liver in response to TNF showed that sulfur amino acids may be partitioned to a greater extent into hepatic protein than into glutathione when sulfur amino acid intake is low. Consequently the adequacy of dietary sulfur amino acids will determine the extent to which antioxidant defenses are maintained during inflammation.

KEY WORDS: • cysteine • methionine • rats • tumor necrosis factor • glutathione

¹ The authors gratefully acknowledge financial support from the Meat and Livestock Commission for the studies reported in this paper.

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ To whom correspondence should be addressed.

Manuscript received 28 October 1993. Revision accepted 27 May 1994.

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