Production of interleukins 10 and 12 by peripheral blood mononuclear cells (PBMC) in chronic hepatitis C virus (HCV) infection.
We previously reported that interferon-gamma (IFN-gamma) production by PBMC in response to HCV core protein was increased in patients with type C chronic liver disease. To understand better the pathophysiology of this disease, we evaluated production of IL-10 and IL-12 by PBMC from 41 patients with chronic HCV infection, including asymptomatic HCV carriers with persistently normal serum ALT values. IL-10 is known to inhibit many effector functions of the immune system, suppressing Th1-type cell development, while IL-12 stimulates differentiation of Th1-type cells, facilitating cell-mediated immunity. IL-10 production was determined by culturing lymphocytes with concanavalin A (Con A), while IL-12 was produced by monocytes in the presence of Staphylococcus aureus Cowan 1 (SAC) with or without recombinant HCV core protein, respectively. The cytokine levels in culture supernatants were measured by ELISA. Spontaneous IL-10 production was greater in patients with chronic hepatitis (CH) (229 +/- 119 pg/ml, P < 0.01) and liver cirrhosis (LC) (185 +/- 88 pg/ml, P < 0.05) than in controls (119 +/- 27 pg/ml), while it was decreased during IFN treatment (70 +/- 25 pg/ml). Both HCV core protein and Con A enhanced IL-10 production by cells from HCV-infected patients. IL-12 was not detectable in medium alone cultures, and SAC-induced IL-12 production did not differ between various patient groups and controls. Simultaneous addition of HCV protein resulted in an increase of IL-12 production in chronic liver disease compared with SAC-alone cultures. Addition of IL-10 to the cultures equally suppressed IFN-gamma production for both controls and patient groups, but the enhancing effect of IL-12 on IFN-gamma production was significantly less in LC than in controls and other patient groups. The findings suggest that secretion of IL-10/IL-12 by cells from control individuals and various patient groups may be different, and that the cytokines might show different effects on IFN-gamma production by some cells.
Kakumu
S
S
First Department of Internal Medicine, Aichi Medical University, Japan.
Okumura
A
A
Ishikawa
T
T
Iwata
K
K
Yano
M
M
Yoshioka
K
K
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D002908:Chronic Disease; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D016174:Hepacivirus / Q000276:immunology; D006526:Hepatitis C / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000276:immunology / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D014758:Viral Core Proteins / Q000494:pharmacology
D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D003208:Concanavalin A; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma