Circulating interferon-α levels and hypertriglyceridemia in the acquired immunodeficiency syndrome

Abstract

The metabolic disturbances seen during infection are thought to be due to cytokines, modulators of the immune response. The acquired immunodeficiency syndrome (AIDS) is characterized by a high prevalence of hypertriglyceridemia and at times depletion of body cell mass (wasting). Elevated circulating levels of cytokines have also been reported in AIDS. Therefore, we determined the relationship between circulating cytokine levels and lipid levels and between circulating cytokine levels and wasting in AIDS and human immunodeficiency virus (HIV) infection. Serum samples from 45 patients with AIDS, 13 subjects with evidence of HIV infection by presence of antibody but without AIDS (HIV positive), and 17 seronegative control subjects who had previously undergone body composition analysis were analyzed for triglyceride, cholesterol, interferon, tumor necrosis factor (TNF), and interleukin-1 levels. Eleven subjects with AIDS or HIV infection had sequential measurements. Interferon was analyzed by bioassay with identification using specific antibodies. TNF and interleukin-1 were assayed by enzyme-linked immunosorbent assay. Lean body mass was assessed by total body potassium. Serum interferon-alpha levels were significantly elevated in patients with AIDS (p less than 0.001 compared to controls), with detectable levels in 84% of AIDS patients. Interferon-alpha was not detectable in serum from controls, while three of 13 HIV-positive subjects had detectable interferon-alpha levels. There was a significant correlation between interferon-alpha levels and serum triglyceride levels in AIDS and HIV-positive patients (R = 0.446, p less than 0.002). There was no relationship between interferon-alpha and serum cholesterol levels (R = -0.039, NS). In contrast only 11% of AIDS patients had detectable circulating TNF levels; the mean value for and the prevalence of detectable serum TNF levels were not significantly different from those of control subjects. Interleukin-1 was not detected in the circulation. There was no correlation between the presence of circulating TNF and serum triglycerides. There was no relationship between circulating interferon-alpha or TNF levels and the presence of wasting as measured by total body potassium. These studies suggest that interferon-alpha, which has previously been shown to modulate lipid metabolism in vivo and in vitro, may be responsible for the hypertriglyceridemia found in AIDS.