Low interleukin-10 production by monocytes of patients with a self-limiting hepatitis C virus infection.
Host factors seem to be crucial for the spontaneous clearance of hepatitis C virus (HCV). Monocytes play a pivotal role in innate immunity and help regulate adaptive responses. This study assesses the characteristics of monocytes from patients with self-limiting HCV infections. We studied 35 consecutive patients [11 with a self-limiting HCV infection, 16 chronically infected with HCV and sustained virological responders (SVR) following antiviral therapy, and eight chronically infected HCV but untreated] and eight healthy donors (HD). The production of interleukin (IL)-10, tumour necrosis factor-alpha (TNF-alpha) and IL-12p40 by monocytes stimulated with lipopolysaccharides(LPS) or HCV Core protein was measured by enzyme-linked immunoassay. Monocyte surface markers were analysed by flow cytometry. LPS and Core protein triggered IL-10 and TNF-alpha production, but monocytes from self-limiting infection patients produced significantly less IL-10 and TNF-alpha than those of SVR, chronically infected or HD (P < 0.05), while IL-12p40 production was unchanged. This cytokine production profile did not appear to be due to expansion of the CD14(+) CD16(+) monocyte subset or to a classical or alternative activation monocyte profile. Monocytes from self-limiting infection patients had more CCR7 than those from SVR or chronically infected patients (P < 0.05). Monocytes of self-limiting infection patients appear to produce little IL-10 and TNF-alpha in response to viral or unspecific stimulation and to have a higher CCR7 expression. This profile seems to be independent to a particular monocyte subset or activation state. Low IL-10 production may help establish an effective immune response and spontaneous HCV clearance.
Martin-Blondel
G
G
EA2405 UMR3 MD-UM-UPS, Université Paul Sabatier Toulouse III, France.
Gales
A
A
Bernad
J
J
Cuzin
L
L
Delobel
P
P
Barange
K
K
Izopet
J
J
Pipy
B
B
Alric
L
L
D000328:Adult; D000368:Aged; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000276:immunology*; D054400:Receptors, CCR7 / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C515370:CCR7 protein, human; C508609:IL10 protein, human; D053762:Interleukin-12 Subunit p40; D054400:Receptors, CCR7; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10