EFFECTS OF DIETARY N-3 FATTY-ACID SUPPLEMENTATION IN MEN WITH WEIGHT-LOSS ASSOCIATED WITH THE ACQUIRED-IMMUNE-DEFICIENCY-SYNDROME - RELATION TO INDEXES OF CYTOKINE PRODUCTION

Cytokines may be involved in weight loss and disturbances of metabolis m associated with human immunodeficiency virus (HIV) infection. Dietar y n-3 fatty acids reduce the production of interleukin-1 (IL-1) and tu mor necrosis factor (TNF) by peripheral blood mononuclear cells (PBMC) in normal humans and prevent IL-1 and TNF anorexia in animals. Accord ingly, we studied the nutritional and metabolic effects of a 10-week t rial of dietary fish oil (MaxEPA 18 g/day) in men with weight loss due to acquired immune deficiency syndrome (AIDS). Twenty men were enroll ed, and 16 completed the 10-week supplementation period. Prior weight loss was 13.7 +/- 1.8 kg (17.4 +/- 1.6% body weight, means +/- SE). Fo od intake, body composition, blood chemistries, serum cytokine concent rations, in vitro production of IL-1 and TNF by PBMC, and clinical cou rse were followed. A subset of subjects (n = 12) underwent stable isot ope infusions to measure de novo hepatic lipogenesis (DNL), an in vivo metabolic index that is influenced by cytokine presence and has previ ously been found to be elevated in AIDS. An unsupplemented group of me n with AIDS wasting (10.4 +/- 2.4 kg weight loss, 13.1 +/- 2.2% body w eight) was monitored for 10 weeks as controls. Baseline food intake (2 ,395 +/- 177 kcal/day and 95.1 +/- 7.2 g protein/day), body weight, pe rcent fat, and fat-free mass were unchanged over the 10-week supplemen tation period. Serum triglycerides were reduced in hypertriglyceridemi c subjects, confirming compliance with fish oil supplementation and su ggesting that their hypertriglyceridemia was at least in part due to o verproduction. Serum TNF and IL-1 were undetectable before or after fi sh oil supplementation. Serum interferon alpha (IFN) was measurable bu t did not change. In vitro production of IL-1 and TNF by PBMC was mark edly reduced both at baseline and after fish oil supplementation in th is population, even in the presence of new AIDS complications compared with normal controls. The metabolic measurement DNL fell and weight w as gained (2.1 +/- 1.3 kg) in subjects who did not develop new AIDS-re lated complications, but further increases in I)NL and further weight loss were observed in subjects who developed a new AIDS complication ( p < 0.05 for interaction between new complication and change in DNL). No changes in body weight, food intake, serum triglycerides, serum cyt okines, or DNL were observed in the unsupplemented group. We conclude that fish oil is a weak anticytokine agent that is unable to overcome the metabolic and nutritional consequences of acute AIDS-related compl ications but may exert a clinical anticytokine effect in stable AIDS p atients. Cytokine production by PBMC is not a useful or reliable marke r of in vivo cytokine activity in AIDS patients with weight loss. In c ontrast, an integrative functional index that is sensitive to cytokine presence in tissues (hepatic DNL) correlated with clinical response. These findings are relevant to the design of future studies of more po tent anticytokine agents, such as thalidomide.