期刊
JOURNAL OF VIRAL HEPATITIS
卷 15, 期 5, 页码 331-338出版社
WILEY
DOI: 10.1111/j.1365-2893.2007.00949.x
关键词
hepatic cytokines; HCV/HIV co-infection; hepatic inflammation; hepatic fibrosis
资金
- NCRR NIH HHS [M01-RR00047] Funding Source: Medline
- NIDDK NIH HHS [DK02573] Funding Source: Medline
Although epidemiologic studies have documented that hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infected patients have accelerated fibrogenesis, especially those with CD4(+) cell counts < 200 cells/mm(3), the pathogenic mechanisms are poorly understood. We investigated whether severe immunodeficiency in co-infection is associated with changes in intrahepatic inflammatory cytokine mRNA levels. We measured interferon (IFN)-gamma, tumour necrosis factor-alpha, transforming growth factor (TGF)-beta(1), interleukin (IL)-4, IL-10, IL-12p35 and IL-12p40 mRNA levels by real-time PCR performed on liver samples from HCV mono-infected (n = 19) and HCV/HIV co-infected (n = 24) patients. Co-infected patients had decreased intrahepatic mRNA levels of IFN-gamma (P = 0.09), IL-4 (P = 0.05) and IL-12p35 (P = 0.04) compared with mono-infected patients, while IL-10 was increased (P = 0.07). In co-infected patients, IFN-gamma mRNA levels increased linearly with increasing peripheral CD4(+) cell counts by 1.23 times relative to the calibrator for every 100 CD4(+) cells/mm(3) increase (P = 0.02). No other cytokines were significantly associated with CD4(+) cell counts. In conclusion, HIV-induced lymphopenia may result in hepatic inflammatory cytokine suppression in HCV/HIV co-infection. Intrahepatic IFN-gamma levels are significantly reduced in patients with advanced immunodeficiency. Further studies are needed to assess whether decreased IFN-gamma secretion by HCV-specific CD4(+) cells may account for accelerated fibrogenesis in these patients.
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