Interferon alfa subtypes and levels of type I interferons in the liver andperipheral mononuclear cells in patients with chronic hepatitis C and controls

Viral infections stimulate the transcription of interferon type I, which in cludes IFN-alfa (IFN-alpha) (13 subtypes) and IFN-beta (a single substance) , Hepatitis C virus (HCV) infection is remarkable by its ability to evade h ost antiviral defenses; however, there is little information as to whether endogenous IFN is activated or not in this disease. Additionally, despite t he fact that the various IFN-alpha subtypes may differ in biological activi ty, there are no data concerning the IFN-alpha subtypes specifically expres sed in normal and diseased liver tissue. Thus, we have analyzed the IFN-alp ha subtypes and the mRNA levels of type I IFNs in samples of normal liver t issue and in liver from patients with chronic hepatitis C. Similar studies were performed in peripheral blood mononuclear cells (PBMC) from patients a nd controls. After amplification and cloning of IFN-alpha cDNA, we observed that 98 of the 100 clones from normal liver tissue corresponded to the IFN -alpha 5 subtype. However, in livers with chronic hepatitis C and in PBMC f rom controls and patients, a variety of subtypes, in addition to IFN-alpha 5, were detected, suggesting a participation of infiltrating leukocytes in the production of IFN-alpha in livers with chronic hepatitis C. As compared with controls, patients with chronic hepatitis C showed a significant incr ease in IFN-beta mRNA in both the liver and PBMC, while IFN-alpha mRNA was significantly increased in PBMC but: markedly reduced in liver tissue. In c onclusion, IFN-alpha 5 is the sole IFN-alpha subtype expressed in normal li ver tissue. The hepatic levels of IFN-alpha are reduced in chronic hepatiti s C, an event that may favor viral persistence.