Relationship of Serum Interleukin-6 and Liver Regeneration after Hepatectomy in N-nitrosodi ethylamine-induced Cirrhotic Rats

ABSTRACT

PURPOSE: The evolution of cirrhosis from chronic inflammatory liver disease represents a dysmorphogenic "response to injury". It is important to understand how inflammatory cytokines, known to be associated with such responses, influence the growth of different cell populations within the liver. The purpose of this work is to establish a role of serum interleukin-6 (IL-6) in liver regeneration following partial hepatectomy in N-nitrosodieth ylamine (DEN)-induced cirrhotic rats. METHODS: Male Sprague-Dawley rats were used for this study. Liver cirrhosis was induced using DEN (100 mg/kg) given once a week for 6 weeks. In Group I (n=18), 70% partial hepatectomy was accomplished and then the resected liver weight, regenerated liver weight, serum IL-6, and serum GOT/GPT was determined on postoperative days 1, 2, and 4 and at intervals. In Group II (n=19), partial hepatectomy was carried out and Laennec, a hepatocyte growth promoter, was injected on preoperative 1 day and postoperative days 1 and 2. RESULTS: The value of serum GOT in Group I was 415 IU/ml on the first postoperative day and peaked at 1870 IU/ml on the third day. In Group II, the level of serum GOT was 404 IU/ml on the first postoperative day and peaked at 593 IU/ml on the third day, then decreased gradually thereafter. The value of serum IL-6 was 106.54 pg/ml on the first postoperative day, 130.59 pg/ml on the 14th postoperative day in Group I, however in Group II, it was 40 pg/ml on thefirst postoperative day and then decreased to 29.18 pg/ml on the 14th postoperative day. The percentages of regenerated weights of liver at intervals following the 70% partial hepatectomy was 55.1% on the first postoperative day, and 102.3% on the 4th week in Group I and 60.4% on the first postoperative day, 95.8% on the first week postoperatively, and 116.1% on the 2nd week in Group II. CONCLUSION: As the value of serum IL-6 was sustained below 40 pg/ml, which was the value on the first postopeative day following partial hepatectomy with Laennec treatment, the resected liver was rapidly regenerated and restored to normal liver function. In cirrhotic liver, regenerative activity was related to serum IL-6 level, so downregulation of serum IL-6 might be helpful to the regeneration of resected liver.