CYSTEINE AND METHIONINE SUPPLEMENTATION MODULATE THE EFFECT OF TUMOR-NECROSIS-FACTOR-ALPHA ON PROTEIN-SYNTHESIS, GLUTATHIONE AND ZINC CONCENTRATION OF LIVER AND LUNG IN RATS FED A LOW-PROTEIN DIET

The synthesis of cysteine-rich compounds such as glutathione and metal lothionein is an integral part of the response to cytokines. To examin e the essentiality of an adequate supply of sulfur amino acids during a response to tumor necrosis factor iv (TNF) we fed rats a low protein (8% casein) diet supplemented with either cysteine and alanine, methi onine and alanine, or alanine alone, or a normal protein (20% casein) diet for 8 d before injection with TNF or saline. Those animals inject ed with saline were pair-fed the intake of their TNF-injected counterp arts for the 24 h after injection. In a second experiment, control gro ups fed the same diets but receiving no treatment were also examined t o establish baseline values. Although few significant differences betw een the non-injected animals consuming food ad libitum were apparent, TNF injection and pair-feeding resulted in differences between the die tary groups. Supplementation of the low protein diet with either cyste ine or methionine improved growth and increased liver and lung glutath ione concentration, zinc concentration, protein concentration and prot ein 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 g roups treated with TNF. The changes in protein synthesis and glutathio ne concentration of the liver in response to TNF showed that sulfur am ino acids may be partitioned to a greater extent into hepatic protein than into glutathione when sulfur amino acid intake is low. Consequent ly the adequacy of dietary sulfur amino acids will determine the exten t to which antioxidant defenses are maintained during inflammation.