Treatment with anti-transforming growth factor β antibodies influences an altered pattern of cytokines gene expression in injured rat liver

The role of transforming growth factor beta(1) (TGF-beta(1)) in mediating hepatic inflammation and regeneration after acute liver injury is beginning to be elucidated, yet its in vivo effect on the gene expression of the major pro-inflammatory and antiinflammatory cytokines produced during that process is unknown. Our previous experiments demonstrated that anti-TGF-beta-treated animals presented profound histological changes as compared with control animals. Therefore, our hypothesis was that by blocking in vivo TGF-beta(1) action, with polyclonal anti-TGF-beta antibodies, we could monitor by RT-PCR significative alterations on the gene expression of IL-1 beta, IL-6, TGF-beta, TNF-alpha, IL-4 and IL-10 in liver-regenerated rats after administration of a single CCl4 dosing. Accordingly, we here report a completely different pattern of cytokines gene expression amidst those groups of rats. Pro-inflammatory cytokines gene expression in control animals showed a clear-cut pattern peaking at 1-2 days postinjury and declining thereafter. Interestingly, IL-6 was present in the control animals only between 12 and 24 h after CCl4 dosing. In the experimental animals, TGF-beta(1) was mainly increased at 4 and 6 days, while IL-6 mRNA was completely absent. IL-1 beta mRNA expression was also altered in the experimental rats, albeit TNF-alpha was nearly unaffected. IL-4 was fully absent in control rats, but remarkably expressed in experimental animals throughout the study. IL-10 was also more expressed in experimental animals. (C) 1998 Elsevier Science B.V. All rights reserved.