Effect of aging and other factors on monocyte aryl hydrocarbon hydroxylase activity

Abstract

A measure of the activity of macrophage drug metabolizing enzymes through assay of peripheral monocytes was used to assess the hepatic enzymatic status and thereby evaluate age related changes in drug metabolism. Blood was obtained from elderly subjects (aged 74.8 ± 5.2, x ̄ ± S.E., n = 16 ) and a young control group (aged 23.5 ± 2.0, n = 27). Monocyte AHH activity was used as an index of liver drug metabolism, ALT activity as an index of liver function, monocyte media IL-1 and as an index of macrophage activation and serum IL-1 levels as a measure of endogenous pyrogenic activity. The medium collected from the cultured monocytes was also assessed for the presence of AHH inhibitory activity. Subjects provided information relating to their age, sex, alcohol consumption, cigarette smoking, recent infection, recent surgery, disease status and medications which could alter drug metabolism. Elderly patients were drawn both from independent seniors living at home and seniors visiting a geriatric day hospital and compared to a control group of young healthy volunteers. Using the experimental design AHH activity did not differ within experimental error between aged (0.832 ± 0.32 nmol/mg prot. per h, n = 16) and young control subjects (if 0.452 ± 0.17, n = 27). ALT activity did not differ between aged (2.83 I.U. ± 0.46) and young (4.24 ± 0.82). Monocyte AHH activity did not differ between males (0.45 ± 0.14, n = 33) compared to females (0.65 ± 0.18, n = 29), but was significantly higher in smokers (2.5 ± 1.0, n = 5) compared to non-smokers (0.35 ± 0.05, n = 52). Mild to moderate alcohol use showed no significant effect on AHH activity. There was no significant difference between the mean level of MCM inhibition of murine hepatocyte AHH between elderly (44.3 ± 8.32%, n = 8) and control (31.5 ± 6.21%, n = 15) subjects, but a larger proportion of the elderly population demostrated such an effect. Serum IL-1 levels (range 0–55.9 pg/ml) were compared to MCM IL-1 and AHH inhibitory activity in the elderly and young group.