Role of heparin on TNF-alpha and IL-6 levels in liver regeneration after partial hepatic resection

The aim of this study was to investigate the effect of heparin on TNF-alpha and interleukin (IL)-6 levels and the complement system in liver regeneration in a murine model.

32 Wistar albino female rats weighing between 180 and 250 g were included in the study. The rats were divided into four groups as follows: group 1, treated with partial (50%) hepatectomy and intravenous heparin 1,000 IU/kg in repeated daily doses; group 2, treated with sham operation and intravenous heparin 1,000 IU/kg in repeated daily doses; group 3, treated with partial (50%) hepatectomy, and group 4 (controls), treated with only sham operation. Before the surgical intervention and after a general anesthetic had been administered to all rats, blood was taken from the left ventricle of each rat, and each sample was assessed to determine total complement hemolytic activity (CH(50)/ml). On the 5th postoperative day, blood was taken to assess CH(50) activity and the levels of TNF-alpha and IL-6 via ELISA. Each rat was then killed by decapitation after which gravimetric analysis and immunohistochemical staining for proliferating cell nuclear antigen (PCNA) were performed.

Serum CH(50) activity of group 1 was 4% as compared to 51% in group 3 (p = 0.01). The serum TNF-alpha level of group 1 was 43 pg/ml as compared to 86 pg/ml in group 3 (p = 0.002). The serum IL-6 level of group 1 was 19 pg/ml as compared to 44 pg/ml in group 3 (p = 0.02). The serum IL-6 level of group 2 was 4 pg/ml as compared to 44 pg/ml in group 3 (p = 0.005). According to the results of gravimetric analysis, the mean regeneration rate of group 1 was 4.4% as compared to 22% of group 3 (p = 0.001). The mean PCNA index values of group 2 was the highest of all groups (p = 0.01). However, the mean PCNA index value of group 1 was the lowest of all groups (p = 0.01).

Because of its anti-inflammatory action via the complement system, heparin produced an unfavorable effect on liver regeneration.