title: Increased serum levels of macrophage inflammatory protein-3alpha in chronic viral hepatitis: prognostic importance of macrophage inflammatory protein-3alpha during interferon therapy in chronic hepatitis C.
abstract: Increased infiltration of lymphocytes and induction of damage and destruction of hepatocytes by these lymphocytes are characteristic features of chronic viral hepatitis. As chemokines attract lymphocytes to inflamed tissues, we studied macrophage inflammatory protein (MIP)-3alpha, a CC chemokine, in chronic viral hepatitis. The levels of MIP-3alpha were measured in the sera from 40 patients with chronic viral hepatitis and 30 control subjects by an enzyme-linked immunosorbent assay (detection limit of MIP-3alpha=7.8 pg/mL). The kinetics of MIP-3alpha were checked during interferon (IFN) therapy in 25 patients. The levels of MIP-3alpha in the sera were significantly higher in patients with chronic viral hepatitis (39.0 +/- 28.9 pg/mL) than control subjects (15.6 +/- 4.9 pg/mL; P < 0.0001) and in patients with severe (49.6 +/- 49.2 pg/mL) and moderate degree of hepatitis (50.9 +/- 27.1 pg/mL) than in mild disease (16.0 +/- 6.8 pg/mL; P < 0.05). A significant correlation was seen among serum MIP-3alpha levels with the levels of alanine aminotransferase (r=0.509, P < 0.0001), aspartate aminotransferase (r=0.505, P < 0.0001), and degrees of activity of hepatitis (r=0.592, P < 0.0001) and interface hepatitis (r=0.419, P=0.0066). The levels of MIP-3alpha were significantly increased in patients with hepatitis C 2 weeks after the start of therapy in IFN-responders, but, remained almost unchanged in IFN-nonresponders. These findings might be important not only for the understanding of immunoptahogenesis of hepatocellular damage in chronic hepatitis (CH) patients but also for a therapeutic strategy to control the local immune response in the liver. A prognostic value of MIP-3alpha during IFN therapy in patients with chronic hepatitis C is also shown.
authors: Third Department of Internal Medicine, Ehime University School of Medicine, Japan.
authors: K
authors: K
authors: Yamauchi
authors: S M F
authors: SM
authors: Akbar
authors: N
authors: N
authors: Horiike
authors: K
authors: K
authors: Michitaka
authors: Morikazu
authors: M
authors: Onji
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000097:blood*; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D008111:Liver Function Tests; D019402:Macrophage Inflammatory Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D054399:Receptors, CCR6; D019707:Receptors, Chemokine
chemical_list: D000998:Antiviral Agents; C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D016898:Interferon-alpha; D019402:Macrophage Inflammatory Proteins; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D016899:Interferon-beta