Differential gene expression of pro-inflammatory and anti-inflammatory cytokines in acute and chronic liver injury

Background: acute carbon tetrachloride (CCl4) intoxication in rats is strongly characterized by the expression of numerous cytokines playing an important role in the pathophysiology of liver diseases. We investigated the chronology of appearance of pro-inflammatory and anti-inflammatory cytokines in the liver of rats treated either acutely or chronically with CCl4. Methods: by using a semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) methodology, we investigated pro-inflammatory and anti-inflammatory cytokines gene expression in liver of rats intoxicated acutely and chronically with CCl4. Results: we found high levels of mRNA transcripts of all pro-inflammatory cytokines [TNF-a, TGF-b, IL-1b, IL-6 and magrophage inflammatory protein-2 (MIP-2)] studied at 24–48 h after acute administration with CCl4, decreasing thereafter and returning to basal levels within 1 week. Specifically, MIP-2 gene expression was detected as early as 6 h after intoxication disappearing at 48 h after treatment. TGF-b was increased at 24 h and peaking at 48 h. IL-10 mRNA was increased at 24 h post-CCl4 and maintained high levels 1 week after intoxication, in spite of the fact, that the inflammatory reaction was already resolved. On the contrary, IL-4 mRNA was not detected at any time analyzed. In chronic damage, pro-inflammatory cytokines gene expression was strong and sustained throughout the study. IL-4 transcripts were not detected. Conclusions: the counterbalance present between the activity of proand anti-inflammatory cytokines in acute damage could be responsible of the control and/or resolution of the inflammatory process. © 1999 Elsevier Science Ireland Ltd. All rights reserved. www.elsevier.com/locate/ihepcom * Corresponding author. Tel./fax: +52-3-6174159. E-mail address: [email protected] (J. Armendáriz-Borunda) 1386-6346/00/$ see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S1386 -6346 (99 )00048 -0 A. Salazar-Montes et al. / Hepatology Research 16 (2000) 181–194 182