interleukin-8 and Hepatitis--Animal

Recombinant human intercrine reduced in hepatomas (hIRH)/stromal cell-derived factor 1 (SDF1-alpha)/pre-B-cell growth-stimulating factor (PBSF), a new chemokine, exhibits an in vitro chemotaxis to neutrophils and a mixed in vivo chemotactic activity to neutrophils, lymphocytes, and monocytes in a rat intradermal injection model. We have investigated the messenger RNA (mRNA) expression of interleukin-8 (IL-8) and hIRH, in chronic hepatitis C of differing severity. Levels of expression of IL-8 and hIRH mRNA obtained from 37 human liver biopsy samples were measured by reverse-transcription and semiquantitative polymerase chain reaction (RT-PCR) amplification. We examined the correlation between mRNA expression and components of the histological activity index (HAI). Patients with HAI > or = 8 had a significantly higher corrected IL-8 mRNA expression ratio (0.24 +/- 0.13 [mean +/- SD]; n = 20) than those with HAI < or = 7 (0.05 < or = 0.03; n = 17; P < .0001). Additionally, IL-8 mRNA expression was strongly associated with the severity of portal inflammation (PI) (high PI vs. low PI, 0.22 +/- 0.14 vs. 0.05 +/- 0.04; P < .0001) and with the presence of bile duct lesions (0.29 +/- 0.15 vs. 0.11 +/- 0.1; P < .01). In contrast, hIRH mRNA expression was not associated with the total HAI, any components of the HAI, or bile duct inflammation or injury. These results suggest that hIRH, although having the -CXC-, alpha chemokine motif, and exhibiting in vivo and in vitro inflammatory activity as does IL-8, plays a different role from IL-8 in hepatic inflammation and injury. IL-8 expression is directly associated with inflammation in patients with chronic hepatitis C, while hIRH expression does not correlate with histopathological severity of inflammation.

Topics: Animals; Chemokine CXCL12; Chemokines, CXC; Chemotactic Factors; Chemotaxis, Leukocyte; Hepatitis C, Chronic; Hepatitis, Animal; Humans; Interleukin-8; Neutrophils; Rats; Recombinant Proteins; RNA, Messenger

Tumor necrosis factor-alpha (TNF) is known to be released after partial hepatectomy. Furthermore, TNF triggers the release of chemotactic cytokines, such as epithelial neutrophil activating protein (ENA-78), which are important for neutrophil chemotaxis, activation, and propagation of the inflammatory response. We now postulate that ENA-78 may play a role the hepatic inflammatory response that occurs following partial hepatectomy. Rats were subjected to 70% hepatectomy or sham laparotomy and were killed in a time-dependent manner. Hepatic neutrophil influx, as assessed by myeloperoxidase (MPO) levels, serum alanine aminotransferase (ALT), and hepatic TNF and ENA-78 levels, as measured by ELISA, were evaluated at 1, 6, and 12 h following operation. MPO levels became significantly elevated within 6 h of hepatectomy and remained elevated at 12 h. Serum ALT became significantly elevated within 1 h of hepatectomy and continued to rise at 12 h. Hepatic TNF and ENA-78 were also increased significantly after hepatectomy. Next, rats undergoing 70% hepatectomy were treated with neutralizing anti-ENA-78 serum; this resulted in a significant decrease in hepatic MPO and serum ALT, suggesting less hepatic injury. To determine whether ENA-78 release was induced by TNF is this model, rats were treated with neutralizing anti-TNF serum and hepatic ENA-78 levels measured 6 h posthepatectomy. ENA-78 levels were significantly decreased in the animals receiving the anti-TNF serum, suggesting that ENA-78 is released in response to TNF in this model. These data suggest that TNF triggers the release of ENA-78 following 70% hepatectomy and that ENA-78 contributes to the hepatic neutrophil influx and liver injury following 70% hepatectomy.

Topics: Alanine Transaminase; Animals; Chemokine CXCL5; Chemokines, CXC; Disease Models, Animal; Hepatectomy; Hepatitis, Animal; Immune Sera; Interleukin-8; Liver; Male; Neutrophils; Peroxidase; Preoperative Care; Rats; Rats, Sprague-Dawley; Time Factors; Tumor Necrosis Factor-alpha; Up-Regulation