Interleukin-8 and hIRH (SDF1-alpha/PBSF) mRNA expression and histological activity index in patients with chronic hepatitis C.

Abstract

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.