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CDI4 is a monocyte/polymorphonuclear cell receptor for lipopolysaccharide (LPS)-LPS Binding Protein (LBP), which mediates most of the toxic effects exerted by such a bacterial component in the host. Here, we provide evidence that sCD14 and interferon (IFN)-gamma serum levels are significantly higher in chronic hepatitis C (CH-C) patients than those detected in normal donors. On the other hand, CD4+/CD8+ antibacterial activity is depressed, thus facilitating entry of bacteria into the host. Of note, all these immune parameters are not modified by in vivo IFN-alpha administration over a period of one year. Finally, after 12 months of IFN-alpha treatment number of CH-C patients with detectable levels of plasmatic LPS increased, thus indicating a continuous release of LPS into the host and also suggesting a putative pathogenetic role for sCD14 LPS-LBP complex in subjects affected by CH-C virus infection.

The immunological effects of interferon (IFN)-alpha administration were evaluated in 15 patients with cHCV infection. Individuals were treated with 6 MU of lymphoblastoid IFN-alpha three times a week for 6 months and with 3 MU three times a week for an additional 6 months. Patients were divided into responders (12 subjects) and nonresponders (3 subjects), respectively, according to alanine aminotransferase serum levels at the end of treatment. Before therapy (T0), absolute numbers of CD3+, CD4+, CD8+, CD14+ and CD16+ cells were significantly reduced in both groups when compared to normal values. At the same time, all patients displayed a profound decrease of phagocytosis and killing exerted by both polymorphonuclear cells (PMN) and monocytes (MO). However, MO Killing resulted to be normal in the responder group. With special reference to T cell function, T cell mediated antibacterial activity, using Salmonella typhi as a target, was also significantly reduced. After therapy (T12), in responder patients a significant increase of CD3+, CD4+, CD14+ and CD16+ cell absolute numbers was observed, while phagocytic and T cell functions were still depressed. Among the nonresponders, in two of three patients IFN-alpha administration gave rise to an increase (above normality) of CD3+, CD4+, CD8+, CD14+, CD16+ and CD20+ cell absolute numbers, while in one patient the same markers dramatically dropped below normal range. In two patients, antibacterial activity was significantly augmented by IFN-alpha treatment, whereas in one patient no modification was observed. Finally, in the same patients IFN-alpha did not correct PMN and MO pretreatment deficits.

In 54 patients with cHCV infection, peripheral immune responsiveness and soluble mediator release were evaluated. Results demonstrate that in these patients phagocytosis and killing capacities exerted by polymorphonuclear cells and monocytes were profoundly depressed. At the same time, absolute numbers of CD3+, CD8+ and CD16+ cells were reduced, while the CD4(+)-CD8+ dependent antibacterial activity was also impaired. With special reference to soluble mediators, elevated amounts of both soluble interleukin-2 receptor and soluble intercellular adhesion molecule-1 were detected in sera of patients. By contrast, serum levels of tumor necrosis factor-alpha were within normal ranges, whereas interferon-gamma serum concentrations were decreased. Of note, in 18.5% of cHCV patients circulating levels of bacterial lipopolysaccharides (LPS) were detected by means of Limulus assay. In the Limulus+subset of patients, absolute numbers of CD14+ cells were reduced in a significant manner, this implying a putative monocyte-LPS interaction. In conclusion, the overall results indicate a condition of peripheral immune depression in cHCV patients with an exaggerated shedding of various mediators endowed with noxious effects for the host.