K. Wadamori et al., INFLUENCE OF CONTINUOUS INTERLEUKIN-2 ADMINISTRATION VIA THE PORTAL-VEIN ON LIVER-REGENERATION FOLLOWING PARTIAL-HEPATECTOMY IN RATS, Hepatology, 23(6), 1996, pp. 1578-1583
We have reported the efficacy of intraarterial-combined immunochemothe
rapy including interleukin-2 (IL-2) for unresectable hepatocellular ca
rcinoma (HCC). To further test this therapy for prevention of intrahep
atic recurrence after hepatectomy, the influence of lL-2 on liver rege
neration was examined using mitotic index (MI) and the bromodeoxyuridi
ne (BrdU) labeling index (LI) in 70% hepatectomized Donryu rats. In ad
dition, gap junction appearance, which may change during liver regener
ation, was analyzed using a monoclonal antibody (HAM8). Serum albumin,
alanine transaminase, and total bilirubin (TB) levels were also evalu
ated. IL-2 (45,000 Japanese reference units [JRU]/d) or saline was adm
inistered continuously via the portal vein immediately after hepatecto
my using an infusion pump. We also examined the influence of IL-2 on L
iver regeneration after hepatectomy with splenectomy. No difference in
the weight of the liver, serum albumin, alanine transaminase, or TB w
as observed in any groups at 1, 2, or 4 days after hepatectomy. Neithe
r IL-2 nor splenectomy influenced MI and BrdU LI at all three points.
Gap junctions began to disappear after hepatectomy and reached a minim
um on day 2 in all groups. Four days after hepatectomy, the density of
the reappearing gap junctions was markedly lower in groups treated wi
th IL-2 than in those receiving saline with or without splenectomy. Ho
wever, the density returned to close to preoperative levels 6 days aft
er hepatectomy in all groups. Continuous portal infusion of IL-2 trans
iently disturbed gap junction reappearance during liver regeneration.
However, no other parameters of Liver regeneration or liver functions
differed. These results suggest that the Liver regeneration after part
ial hepatectomy may be suppressed by the administration of IL-2, even
though the suppression may not be harmful for overall recovery of the
resected liver. However, it seems that hepatic IL-2 administration can
be performed without serious complications after hepatectomy.