Induction of interleukin-6 by hepatitis C virus core protein in hepatitis C-associated mixed cryoglobulinemia and B-cell non-Hodgkin's lymphoma.

Abstract

PURPOSE:

Chronic hepatitis C carries the risk to develop mixed cryoglobulinemia (MC) and B-cell non-Hodgkin's lymphoma (B-NHL), possibly because viral antigens stimulate the host's inflammatory response via extracellular pattern recognition receptors (PRR). To clarify this issue, we studied whether recognition of hepatitis C virus (HCV) proteins by PRR is involved in the pathogenesis of HCV-associated MC or B-NHL.

EXPERIMENTAL DESIGN:

Peripheral blood mononuclear cells of patients with HCV-associated B-NHL (n = 12), MC (n = 14), uncomplicated hepatitis C (n = 12), and healthy volunteers (n = 12) were incubated with the recombinant HCV proteins E2, core, and NS3 to study induction of cytokine production, stimulation of B-cell proliferation, and immunoglobulin secretion. In addition, serum levels of interleukin-6 (IL-6) were measured by ELISA.

RESULTS:

HCV core was the only studied protein, which induced production of IL-6 and IL-8 in CD14(+) cells. IL-6 induction was mediated via Toll-like receptor 2 (TLR2) and lead to increased B-cell proliferation in vitro. TLR2 expression on monocytes and IL-6 serum concentrations were increased in all groups of HCV-infected patients compared with healthy controls and were highest in MC (P < 0.05).

CONCLUSIONS:

Increased secretion of IL-6 via stimulation of TLR2 by HCV core protein may play a role in the pathogenesis of hepatitis C-associated MC and B-NHL.

• Authors: Georg Feldmann, Hans Dieter Nischalke, Jacob Nattermann, Brigitte Banas, Thomas Berg, Christian Teschendorf, Wolff Schmiegel, Ulrich Dührsen, Juliane Halangk, Agathe Iwan, Tilman Sauerbruch, Wolfgang H Caselmann, Ulrich Spengler
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 12 Issue 15 Pg. 4491-8 (Aug 01 2006) ISSN: 1078-0432 [Print] United States
• PMID: 16899594 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-6
• Interleukin-8
• Recombinant Proteins
• TLR2 protein, human
• Toll-Like Receptor 2
• Viral Core Proteins

Topics

• Adult
• Aged
• Aged, 80 and over
• Cell Proliferation
• Cryoglobulinemia (blood, etiology)
• Female
• Hepacivirus (immunology)
• Hepatitis C (blood, complications, immunology)
• Humans
• Interleukin-6 (biosynthesis, blood)
• Interleukin-8 (biosynthesis)
• Leukocytes, Mononuclear (immunology)
• Lymphoma, B-Cell (blood, etiology)
• Lymphoma, Non-Hodgkin (blood, etiology)
• Male
• Middle Aged
• Recombinant Proteins (blood, metabolism)
• Toll-Like Receptor 2 (genetics, metabolism)
• Up-Regulation
• Viral Core Proteins (immunology)