Interleukin-12 p40/p70 ratio and in vivo responsiveness to IFN-alpha treatment in chronic hepatitis C.
To evaluate the relationship between cytokine balance and responsiveness to interferon-alpha (IFN-alpha), we investigated the production of IFN-gamma, interleukin-10 (IL-10), IL-12 p70, and IL-12 p40 by peripheral blood mononuclear cell (PBMC) cultures from patients with chronic hepatitis C (CHC) before and after 1 year of IFN-alpha treatment. Before the therapy, responder (R) patients exhibited lower IFN-gamma release, higher IL-10 production, and higher values of the IL12 p40/p70 ratio compared with nonresponders (NR). Increased sensitivity to the effects of IL-12 and IL-10, as well as higher IL-12-dependent IFN-gamma secretion, were also found in the R subset. After IFN-alpha therapy, an increase in IFN-gamma production and a decrease in the IL-12 p40/p70 ratio were observed in R patients, whereas opposite results were obtained in the NR group. Finally, the therapy induced downregulation of IL-10 production and cell responsiveness to recombinant IL-12 in all patients. These findings imply that predominance of a T helper 2 (Th2) cytokine profile in CHC patients favors the beneficial effects of IFN-alpha, thus suggesting a therapeutic role for Th1-driven stimulation of immune response. The findings also stress the primary importance of the IL-12 p40 and p70 balance in the modulation of immune responses to hepatitis C virus (HCV).
Piazzolla
G
G
Department of Internal Medicine, Immunology and Infectious Diseases, University of Bari Medical School, Bari, Italy. g.piazzolla@intmed.uniba.it
Tortorella
C
C
Fiore
G
G
Fanelli
M
M
Pisconti
A
A
Antonaci
S
S
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000998:Antiviral Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000821:virology; D018417:Th1 Cells / Q000187:drug effects / Q000821:virology; D018418:Th2 Cells / Q000187:drug effects / Q000821:virology
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D016207:Cytokines; D016898:Interferon-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma