INFLAMMATORY CYTOKINES AND TYPE-I 5'-DEIODINASE EXPRESSION IN PHI(1) RAT-LIVER CELLS

Administration of tumour necrosis factor-alpha (TNF alpha), interleuki n-1 beta (IL-1 beta) and interleukin-6 (IL-6) to animals and humans re sults in changes in circulating thyroid hormone concentrations similar to those seen in non-thyroidal illness (NTI). Inflammatory cytokines have been postulated as mediators of the euthyroid sick syndrome by in hibiting type 1 5'-deiodinase (5'D-I) enzyme activity. We have investi gated direct effects of cytokines upon 5'D-I expression, measuring cha nges in 5'D-I enzyme activity and mRNA in Phi(1) rat liver cells. All three cytokines stimulated 5'D-I enzyme activity: TNF alpha 326 +/- 43 % (100% in controls, mean + S.E.M., n = 9, P < 0.01 by ANOVA), IL-1 be ta 297 +/- 8% and IL-6 272 +/- 25%. Co-incubation with cycloheximide a bolished stimulation by each cytokine. Kinetic analysis revealed that stimulation of 5'D-I enzyme activity was a result of significantly inc reased V-max, (P <0.01 by ANOVA) with K-m relatively unchanged. 5'D-I mRNA abundance was not significantly changed following treatment by an y of the three cytokines. These findings do not support the hypothesis that inflammatory cytokines may mediate the euthyroid sick syndrome b y causing inhibition of 5'D-I activity. (C) 1997 Elsevier Science Irel and Ltd.