creases in soluble immune factors, such as serum An imbalance between T helper cell (Th)1 and Th2interleukin-2 (IL-2) receptor have provided peripheral evilike cytokines has been described in several chronic dence that significant intrahepatic anti-HCV immune proinfectious diseases. We therefore analyzed the intrahecesses may be occurring. 4 However, there is a paucity of patic messenger RNA (mRNA) expression of Th1-like (indata relating to the intrahepatic expression of cytokines that terleukin [IL]-2, interferon [IFN]-g) and Th2-like (IL-4, may be expected to mediate any immune response in the IL-10) cytokines in chronic hepatitis C patients (n Å 17) liver in chronic HCV infection. and controls (n Å 6) and correlated the results with liver
Cytokines are regulatory molecules that play an important histology and intrahepatic viral load. Intrahepatic cytorole in many physiological and pathological processes. CD4/ kine mRNA and hepatitis C virus (HCV) RNA were quan-T cells, which are central to the induction of anti-viral retitatively assessed by polymerase chain reaction (PCR) sponses, have been subdivided according to two predominant using a dot-blot hybridization technique. Liver biopsy cytokine secretion profiles originally described in mouse Tspecimens were histologically graded using the Scheuer cell clones. 5 T helper (Th) 1 cells produce cytokines such as Score. IFN-g and IL-2 mRNA expression were signifi-IL-2 and interferon-g (IFN-g) which are important factors cantly upregulated in chronic HCV vs. controls (P õ .002, responsible for promoting the cell-mediated immune re-P õ .04, respectively). Both correlated significantly with sponse. In contrast Th2 cells produce cytokines such as IL-4 histological fibrosis and portal tract inflammation. In contrast, the expression of IL-10 mRNA was decreased and IL-10, which mediate the humoral response. However, in cirrhosis and chronic HCV compared with controls (P it is now recognized that these cytokines can be produced õ .02, P õ .0001, respectively). IL-4 mRNA was detected by cells other than CD4/ T cells and therefore it has been inconsistently at low levels in all groups. Intrahepatic suggested that these polarized cytokine responses be referred viral load did not correlate with either cytokine expresto as Th1-like or type 1 and Th2-like or type 2 responses. 6 sion or tissue injury. In conclusion, the progressive liver Recently the relationship of Th1 versus Th2-like cytokines injury seen in chronic HCV is associated with the upregin chronic infections such as human immunodeficiency virus, ulation of intrahepatic Th1-like cytokines and the downleprosy, and leishmaniasis has been explored. [6][7][8][9][10] A decrease regulation of IL-10, a Th2-like cytokine. These results in cell-mediated immunity, i.e., a Th2-type profile, has been suggest a role for delayed-type hypersensitivity immune suggested to be associated with increased pathogen load and reactions in HCV related liver injury. (HEPATOLOGY progressive disease. It is unknown whether chronic HCV in-1996;24:759-765.) fection conforms to this paradigm. We used a quantitative polymerase chain reaction (PCR) method to identify the intrahepatic messenger RNA (mRNA) The mechanism responsible for hepatocellular injury in expression of Th1-like versus Th2-like cytokines in chronic chronic hepatitis C virus (HCV) infection is currently un-HCV. The results show that there is an increase in mRNA clear. It is unknown whether HCV produces liver cell damexpression of IL-2 and IFN-g in chronic HCV infection, which age through a direct cytopathic effect or as a by-product of correlates with disease severity and liver damage. In conthe intrahepatic anti-HCV immune response. 1,2 A role for trast, there was very low expression of IL-4 mRNA in all anti-HCV immune mediated liver cell damage has been sugspecimens and downregulation of IL-10 mRNA in hepatitis C gested by immunohistochemical studies showing the upregspecimens compared with controls. There was no correlation ulation of cytokine-dependent adhesion molecules. 3 Inbetween cytokine mRNA expression and viral load. In view of the results we suggest that the progressive liver injury seen in chronic HCV may be related to an upregulation of Abbreviations: HCV, hepatitis C virus; IL, interleukin; Th, T helper; IFN-g, interferon-cell-mediated responses that apart from their antiviral efg; PCR, polymerase chain reaction; mRNA, messenger RNA; cDNA, complementary DNA; fects may also lead to nonspecific tissue damage. If so, this ALT, alanine transaminase; SS, Scheuer score.