Changes of serum cytokines and expression of inducible nitric oxide synthase mRNA by Kupffer cells after relief from obstructive jaundice in rats.

AIMS

To investigate the changes of serum endotoxin, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS) expression by Kupffer cells after relief of obstructive jaundice (OJ) by internal biliary drainage (ID) and external biliary drainage (ED) in rats.

MATERIALS AND METHODS

Forty eight adult Sprague Dawley rats were randomly assigned to four groups: OJ, ID, ED and sham operation (SH). Inducible nitric oxide synthase mRNA by the Kupffer cells was detected by reverse transcription polymerase chain reaction. The serum TNF-alpha and IL-6 were measured by enzyme linked immunosorbent assay and endotoxin by kinetic turbidimetric limulus tests.

RESULTS

Serum endotoxin, IL-6 and TNF-alpha levels were significantly elevated in OJ rats compared to that of SH rats (P < 0.01). After relief from OJ, the elevated endotoxin, IL-6 and TNF-alpha levels could be significantly depressed by ID (P < 0.01). However, the serum IL-6 level was increased in ED rats (P < 0.05) and the TNF-alpha level was not depressed by ED. Expression of iNOS mRNA by Kupffer cells was markedly stronger in the OJ group than in the SH group (P = 0.005). After relief from OJ, the iNOS mRNA expression was suppressed by ID (P = 0.139, ID vs OJ). However, the iNOS mRNA expression was promoted by ED (P = 0.321 ED vs OJ; P = 0.016 ED vs SH).

CONCLUSIONS

The levels of serum endotoxin, TNF-alpha and IL-6 and the expression of iNOS mRNA by Kupffer cells were increased in rats with obstructive jaundice. Internal biliary drainage could entirely reverse the changes, but external drainage only partially did.