Interleukin-1alpha and tumor necrosis factor alpha modulate cytochrome P450 activities in carp (Cyprinus carpio).

ABSTRACT

In mammals, it has been shown that the activation of host defense mechanisms down-regulates microsomal cytochrome P450 by the liberation of cytokines. We investigated the effect of interleukin-1alpha (IL1alpha) and tumor necrosis factoralpha (TNFalpha) on constitutive and 3-methylcholanthrene (3-MC)-induced biotransformation activities in carp. We have first measured the time course response of ethoxyresorufine O-decthylase (EROD) activity in liver, head kidney, and spleen 1, 2, 3, 5, and 7 days after intraperitoneal injection of a prototypical Cyp 1A inducer (3-MC). This activity was compared to the rate of 3-MC accumulation in all organs tested. A correlation between a diminution of EROD activity and an increase in 3-MC concentration in each organ was observed. We have also tested the effects of two inflammatory cytokines (IL1alpha and TNFalpha) on biotransformation activities. Intravenous injection of these compounds resulted in a marked depression of 3-MC-induced glutathione S-transferase activity in all organs tested and in 3-MC-increased cytochrome P450 content in the liver and head kidney. TNFalpha produced an increase in basal EROD activity in the liver and head kidney. Taken together, these results suggested that, as in mammals, the activation of host defense mechanisms regulates microsomal cytochrome P450 and related enzymes in fish.