Involvement of innate immunity in the pathogenesis of chronic hepatitis C in children.
The aim of the study was to assess the role of selected elements of innate immunity in the pathogenesis of chronic hepatitis C in children. The study comprised 20 children with chronic hepatitis C (group 1), nine healthy hepatitis C virus (HCV) seropositive children (group 2) and 18 healthy children (control group). We evaluated the expression of Toll-like receptor (TLR)2 and TLR4 on peripheral blood neutrophils, and generation of interleukin (IL)-8, IL-10, IL-12 and reactive oxygen species (ROS) by neutrophils. The performed tests demonstrated higher expression of TLR2 and TLR4 on stimulated neutrophils and of TLR4 on non-stimulated neutrophils in group 1 in comparison to HCV seropositive children and controls. In group 1, the expression of TLR2 after granulocyte colony-stimulating factor (GCSF) stimulation showed positive correlation with alanine aminotransferase and asparate aminotransferase activities, while the expression of TLR2 without stimulation and of TLR4 after GCSF stimulation also correlated with necrosis. IL-12 generation by lipopolysachcharide-stimulated neutrophils was higher in group 1 versus controls. In group 1, maximum chemiluminescence (CL) without pre-activation, both spontaneous and after formyl-methionyl-leucyl-phenylanine and phorbol-myristate-acetate (PMA) stimulation, was significantly lower than in the controls. CL after tumour necrosis factor-alpha pre-activation and PMA stimulation was still lower than in the controls, however, after opsonized zymosane stimulation it was significantly higher than in the controls. Our studies suggest the involvement of neutrophils in the pathogenesis of chronic hepatitis C in children. Neutrophils demonstrate increased expression of TLR2 and TLR4 (correlating with the features of hepatocytic damage and intensification of necrosis), inhibition of oxygen metabolism, and after TNF-alpha pre-activation higher ability to produce ROS.
Wisniewska-Ligier
M
M
3rd Department of Paediatrics, Polish Mother's Memorial Hospital, Research Institute, Lodz, Poland.
Wozniakowska-Gesicka
T
T
Glowacka
E
E
Lewkowicz
P
P
Banasik
M
M
Tchorzewski
H
H
D000293:Adolescent; D002478:Cells, Cultured; D002648:Child; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000821:virology; D010100:Oxygen / Q000097:blood / Q000378:metabolism; D013481:Superoxides / Q000097:blood / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000097:blood; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000097:blood
D016207:Cytokines; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D013481:Superoxides; D010100:Oxygen