Interleukin-10 induction after combined resection of liver and pancreas.
OBJECTIVE
Recently in Japan, combined resection of liver and pancreas is being performed in cases of advanced biliary neoplasms. As we previously reported, in the rat model of combined resection of the liver and pancreas, the potential for liver regeneration after this operation was decreased compared to that after hepatectomy only. Moreover, non-parenchymal cells play an important role in the production of inhibitory factors for liver regeneration. The anti-inflammatory cytokine IL-10, downregulates the release of TNF-alpha, and affects the progressive regeneration of the hepatic parenchyma. To investigate the role of IL-10 and TNF-alpha in hepatic regeneration in the rat, we measured the levels of IL-10 and TNF-alpha in the conditioned medium of non-parenchymal cells stimulated with portal plasma. We also investigated the concentration of IL-10 and TNF-alpha in the portal plasma after combined resection of the liver and pancreas.


METHODS
Adult male Sprague-Dawley rats were used. Rats were divided into 3 groups: group I underwent 70% partial hepatectomy only (Hx), group II underwent 70% partial pancreatectomy only (Px) and in group III both procedures were used, Hx plus Px (HPx). Portal plasma was harvested at 1, 3, 6, 12 and 24 hours after surgery and was used to stimulate the culture medium of non-parenchymal cells. Cytokine concentrations in the plasma and in the conditioned medium were measured by ELISA. Northern blot analysis for IL-10 mRNA was performed on liver, pancreas, kidney, lung and spleen at 1, 3 and 6 hours after surgery.


RESULTS
The level of IL-10 released by non-parenchymal cells stimulated with HPx portal plasma was 154.1 +/- 20.3 pg/mL and significantly higher than when stimulated with Hx portal plasma, which was 100.1 +/- 6.4 pg/mL (P < 0.05) during the first hour. Also, the level of TNF-alpha released by Kupffer cells stimulated with HPx portal plasma was 86.6 +/- 13.4 pg/mL, significantly less than when stimulated with Hx portal plasma, which was 138.7 +/- 15.1 pg/mL (P < 0.005) during the first hour. Furthermore, the plasma levels of IL-10 in the HPx group remained significantly higher than those of the other groups from 6 hours up to 12 hours. In northern blot analyses, higher IL-10 mRNA expression were detected in the spleen and moderately high levels in the liver at 1 and 3 hours after HPx, in contrast to those after Hx.


CONCLUSIONS
IL-10 expression is induced in the spleen and liver remnant just after HPx. IL-10 released by the spleen and liver might downregulate TNF-alpha production, thereby inhibiting the liver regeneration.
Uchiyama
T
T
First Department of Surgery, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574 Sendai, Miyagi, Japan.
Suzuki
M
M
Unno
M
M
Rikiyama
T
T
Oikawa
M
M
Matsuno
S
S
D000818:Animals; D017077:Culture Media, Conditioned; D015536:Down-Regulation / Q000502:physiology; D006498:Hepatectomy; D016753:Interleukin-10 / Q000378:metabolism*; D007728:Kupffer Cells / Q000502:physiology; D008115:Liver Regeneration / Q000502:physiology; D008297:Male; D010180:Pancreatectomy; D011184:Postoperative Period; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D017077:Culture Media, Conditioned; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10