EXPRESSION OF CYTOKINE GENES DURING LIVER-REGENERATION AFTER PARTIAL-HEPATECTOMY IN RATS

In the present study to demonstrate the relationship between cytokines and liver regeneration we investigated by Northern blot hybridization the cytokine gene induction in the regenerating liver and several oth er organs (spleen, lung, and kidney) in the rat after partial hepatect omy (PH). We also examined whether Kupffer cells and the spleen are in volved in the induction of cytokine mRNA in the regenerating liver. Bo th IL-1 alpha and beta mRNA increased transiently 1/2 to 1 hr after PH in nonparenchymal cells (NPC) of the regenerating liver; they reached a maximum before the peak of hepatocyte DNA synthesis. PH also induce d a slight, but significant, gene expression of IL-1 in lung and kidne y in the early postoperative period. TNF-alpha mRNA increased graduall y in the spleen, but not the liver, of partially hepatectomized rats a t 3 to 12 hr and then reached a peak at 24 hr after PH. IL-6 transcrip ts were not detected in the regenerating liver, spleen, lung, or kidne y during liver regeneration. In contrast, no cytokine gene expression was induced in any of these four organs during the first 3 days after sham operation or unilateral nephrectomy. When Kupffer cell activity w as suppressed by gadolinium chloride pretreatment, or when splenectomy was performed 24 hr before PH, the constitutive IL-1 alpha and beta m RNA expressions in NPC of the normal rat liver were completely suppres sed. In conclusion, the present study demonstrates, for the first time , the specific kinetics of cytokine gene expression in the liver, sple en, lung, and kidney after PH. Further studies on the role of cytokine gene induction should contribute to an understanding of the pathophys iology of liver regeneration. (C) 1995 Academic Press, Inc.