Inhibition of immune activation, impairing either the cellular (thymectomy) or the cytokine respone (application of anti-inflammatory cytokine G-CSF), is enhancing liver regeneration

Recently, we raised the hypothesis, that liver regeneration is inversely correlated with parameters of immune activation. This was the reason to test on one hand the effect of thymectomy, which is impairing T-cell maturation and subsequent T-cell activation. As GCSF was reported to have anti-inflammatory activity affecting cytokine release, the effect of the perioperative treatment with GCSF on liver regeneration was investigated in a second approach.

Rats were subjected to 90% partial hepatectomy. Animals were sacrificed 24h, 48h and 7 days after resection. Besides the survival time and rate, read-out parameters were liver damage in terms of liver enzymes and histomorphological alterations. Hepatic regeneration was determined by measuring the hepatocyte BrdU Labeling index and by assessing the liver weight recovery.

Survival rate was slightly increased in both -treatment groups, however this effect was not statistically significant. Liver damage in terms of liver enzymes was significantly lower after thymectomy as well as in the GSCF-treatment group. Similarly, morphological signs of liver damage were less pronounced in the treatment groups. BrdU-LI was not different but full liver weight recovery within one week was only achieved in the treatment groups indicating an enhanced regenerative response.

Both completely different approaches to impair immune activation and the release of proinflammatory cytokines, did improve the damage to the remnant liver and enhanced the regenerative potential of the remnant liver. These observations support the perception that the inflammatory response caused by the resection procedure itself, is impairing the regenerative response. In contrast, reduction of the postoperative inflammation is enhancing the course of liver regeneration, thus supporting the hypothesis.