Influence of Continuous Interleukin–2 Administration Via the Portal Vein on Liver Regeneration Following Partial Hepatectomy in Rats

Abstract

suppression may not be harmful for overall recovery of We have reported the efficacy of intraarterial-comthe resected liver. However, it seems that hepatic IL-2 bined immunochemotherapy including interleukin-2 administration can be performed without serious com-(IL-2) for unresectable hepatocellular carcinoma (HCC).plications after hepatectomy. (HEPATOLOGY 1996;23:1578-To further test this therapy for prevention of intrahe-1583.) patic recurrence after hepatectomy, the influence of IL-2 on liver regeneration was examined using mitotic index (MI) and the bromodeoxyuridine (BrdU) labeling index Although significant progress has been made in the (LI) in 70% hepatectomized Donryu rats. In addition, gap surgical treatment of human hepatocellular carcinoma junction appearance, which may change during liver re-(HCC), as well as in the detection of small HCC with generation, was analyzed using a monoclonal antibody diagnostic techniques such as ultrasonography and (HAM8). Serum albumin, alanine transaminase, and tocomputed tomography, cancer recurrence, including intal bilirubin (TB) levels were also evaluated. IL-2 (45,000 trahepatic recurrence, is observed in about 50% of pa- Japanese reference units [JRU]/d) or saline was admin-istered continuously via the portal vein immediately tients with HCC in the year following hepatic resecafter hepatectomy using an infusion pump. We also ex-tion. 1 Most of the recurrences involve the remnant amined the influence of IL-2 on liver regeneration after liver, with intrahepatic metastasis occurring via the hepatectomy with splenectomy. No difference in the portal tract. [1][2][3] weight of the liver, serum albumin, alanine transamiSince 1988, we have performed continuous intrahenase, or TB was observed in any groups at 1, 2, or 4 patic administration of interleukin-2 (IL-2) combined days after hepatectomy. Neither IL-2 nor splenectomy with anticancer agents for the treatment of unresectinfluenced MI and BrdU LI at all three points. Gap junc-able HCC with satisfactory response. The response rate tions began to disappear after hepatectomy and reached was 58.3%, including four cases of complete response. a minimum on day 2 in all groups. Four days after hepa-The overall 2-year survival rate was 52% and the 2-tectomy, the density of the reappearing gap junctions was markedly lower in groups treated with IL-2 than year survival rate of responders was 80%. 4 Before this in those receiving saline with or without splenectomy. therapy is introduced to prevent intrahepatic recurHowever, the density returned to close to preoperative rence, the influence of IL-2 on liver regeneration should levels 6 days after hepatectomy in all groups. Continu-be evaluated, although we experienced no severe side ous portal infusion of IL-2 transiently disturbed gap effects concerning hepatic function in our clinical protojunction reappearance during liver regeneration. How-col. A previous experimental study reported that ILever, no other parameters of liver regeneration or liver 2 exerts inhibitory influence ...

IL‐2/IL‐6 ratio correlates with liver function and recovery in acute liver injury patients

“…Alternatively, IL‐2 may induce regulatory T cells, which inhibit the effect of IL‐6 and/or of IL‐17 on immune status . After the injury is resolved, IL‐2 or IL‐6 may also regulate the recovery of liver function and the regeneration of hepatocytes . Ling and Puel (2014) demonstrated that IL‐6 induces IL‐17, which in turn may improve the tissue regeneration through TGF‐β–MMP‐9 (matrix metalloproteinase 9) signaling .…”

Regeneração hepática: papel dos fatores de crescimento e nutrientes

“…O desempenho adequado da regeneração hepática, é complexo e dependente da interação de eventos, que envolve a regulação da matriz extracelular, espaçamento do intervalo de junção intercelular, dissolução e ressíntese da membrana altamente especializada dos hepatócitos, além da liberação e alinhamento de mais de 150 cromossomos, entre os quais alguns que proporcionam a mitose 27,10,21 . Durante a regeneração, tanto os fatores de crescimento, como as alterações metabólicas, podem induzir o período de iniciação.…”

“…O provável mecanismos de ação envolve redução do intervalo de junção dos hepatócitos, dificultando trocas de substancias hepatotróficas entre as células e redução do índice mitótico. No entanto, os autores reportam que o tratamento com IL-2 não é suficiente para provocar sérias complicaçoes após a HP, ou até mesmo interromper totalmente o processo de regeneração hepática 27 .…”

Influência da infusão parenteral de aminoácidos sobre a expressão gênica de fatores de crescimento de timidina quinase no remanescente hepático de ratos desnutridos

“…Existe relação entre citocinas pró-inflamatórias e a via de sinalização imediata que induz a regeneração hepática após HP. No fígado as citocinas são produzidas por monócitos, macrófagos e células endoteliais em resposta à lesão tecidual (Michaloupoulos e DeFrances, 1997;Wadamori et al, 1996;Arias et al, 1994;LaBrecque, 1994).…”