Depression of peripheral blood monocyte aryl hydrocarbon hydroxylase activity in patients with liver disease: Possible involvement of macrophage factors

Aryl hydrocarbon hydroxylase activity was detectable in cultured macrophage monolayers of peripheral blood monocyte origin. Peripheral blood monocytes were isolated from patients with biopsy‐confirmed liver disease and healthy volunteers. Macrophage monolayers were prepared and incubated at 37°C. After 24 hr, the aryl hydrocarbon hydroxylase activity and cellular protein concentration were assayed on cell homogenates. The monocyte aryl hydrocarbon hydroxylase activity in cultured macrophages from normal volunteers was 1.23 ± 0.16 (n = 19). The aryl hydrocarbon hydroxylase activity in macrophage cultures from patients with biopsy‐confirmed liver disease was 0.48 ± 0.05 (n = 20). This represents a significant (61%) decrease in monocyte aryl hydrocarbon hydroxylase compared to controls. The 20 patients have established cirrhosis or early stage liver disease. The established cirrhosis group includes α₁‐antitrypsin deficiency‐associated cirrhosis; primary biliary cirrhosis; alcoholic (Laennec's) cirrhosis; cryptogenic cirrhosis, and hemochromatosis. Early stage liver disease is attributed to methotrexate (Stage III), early stage primary biliary cirrhosis and α₁‐antitrypsin deficiency. Our results indicate that the depression in monocyte aryl hydrocarbon hydroxylase activity is greater in patients with established cirrhosis than early stage liver disease. Our results further suggest that cultured monocytes from patients with liver disease spontaneously release soluble factors into the culture medium. Incubation of this medium, containing macrophage factors, with isolated hepatocytes significantly depress hepatocyte aryl hydrocarbon hydroxylase activity compared to medium obtained from cultures of monocytes from normal volunteers. We propose that cultured monocyte aryl hydrocarbon hydroxylase activity mimics the hepatic enzyme and reflects the status of the hepatic enzyme in severe liver disease. Consequently, monocyte aryl hydrocarbon hydroxylase activity may be a useful noninvasive measure of hepatic enzyme function.