An experimental study of a splenic inhibitory factor influencing hepatic regeneration.

The effect of splenectomy on hepatic regeneration after 70 per cent partial hepatectomy was studied in rats. Compared with nonsplenectomized rats, preliminarily splenectomized rats showed significantly increased weights of the liver in the early stage (up to four days) after hepatectomy and significantly promoted deoxyribonucleic acid synthesis in the regenerating liver in terms of high levels of 3H-thymidine uptake, thymidine kinase activity and mitotic index in the residual liver 24 hours after hepatectomy. The splenic factor inhibiting hepatic regeneration, as previously suggested, was investigated by using primary cultures of rat hepatocytes. At 48 hours when the 3H-thymidine uptake by cultured hepatocytes reached maximum, the group containing a splenic extract showed significantly lower levels (p less than 0.005) of uptake than did the group without the extract and the group containing splenic venous serum also showed lower levels. This splenic factor was labile against heat and lost activity by trypsinization. Furthermore, gel filtration by the use of Sephadex G-75 column suggested the factor to be a protein-like substance with a molecular weight of 50,000 to 60,000. It is likely that a protein-like substance inhibiting hepatic regeneration after hepatectomy is present in the spleen.