T helper type 1 (Th1) cytokines play an important role in antiviral defence. The purpose of this study was to quantify by ELISA IL2, soluble receptor of IL2 (IL2Rs), IFNgamma TNFbeta, IL4, IL6 and IL10 levels in the sera of 134 HCV-positive patients, 69 of whom were coinfected with HIV, and in 54 HIV-HCV-negative patients. The mean IL2Rs and IFN serum levels were much higher in patients with anti-HCV than in the control group, whereas the mean IL4 and IL6 levels were lower in patients infected with HCV. There were no significant differences in cytokine levels between patients with and without HIV. There were significantly less patients with HCV than controls with IFNgamma levels under cut-off, and significantly more patients with HCV with IL4 levels under cut-off. Although serum level of cytokines must be interpreted with caution, the results suggest that Th1 response is enhanced in HCV infection.
"Findings from our study are consistent with those from prior studies investigating the association between HIV/HCV status and TNF-α [27-30], CRP [31,32], IL-10 [30,33], IFN-γ [30,34,36], IL-6  and cystatin C . However, some differences between our work and these prior studies may reflect different biomarker outcome categorization (quartiles versus detection, secretion, or means), HIV/HCV categorization (viremia versus antibody detection, in vitro stimulation with viral proteins) sources of biomarkers (serum versus intrahepatic), referent groups (participants with undetectable HIV and HCV viremia versus HIV or HCV mono-infected participants) and adjustment covariates. "
[Show abstract][Hide abstract] ABSTRACT: Assessing whether hepatitis C (HCV) co-infection with human immunodeficiency virus (HIV) is associated with increased inflammation is complex. The liver, integral to inflammatory biomarker synthesis, is compromised by HCV and alcohol abuse. Using single liver-synthesized biomarkers (e.g. C-reactive protein) to represent inflammation may not be appropriate in HIV/HCV co-infection. We hypothesized that 1) detectable HIV/HCV RNA was independently associated with increased inflammation; 2) a composite inflammation measure describes inflammation differently from single inflammatory biomarkers.
We compared inflammation by HIV/HCV group in a cohort of 361 HIV infected participants from the HIV-Longitudinal Interrelationships of Viruses and Ethanol study. Inflammatory biomarkers >75th percentile were considered elevated. Associations between HIV/HCV group and elevated biomarkers were analyzed as a composite measure (inflammatory burden) or individually. We defined inflammatory burden as number of concurrently elevated biomarkers. Biomarkers included interleukin-6 (IL-6), C-reactive protein (CRP), cystatin C, serum amyloid-A (SAA), tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10). Covariates: alcohol, liver fibrosis, comorbidities, CD4 count, antiretroviral therapy, substance use.
Detectable HIV and HCV RNA (OR = 2.49; 95%CI = 1.05--5.89) and detectable HCV RNA alone (2.95; 1.08--8.01) were independently associated with increased odds of having a greater inflammatory burden compared to undetectable viremia. Elevated IL-10 (7.79; 1.90--31.97) and TNF-alpha (7.70; 1.42--41.83) were independently associated with detectable HIV and HCV RNA. Elevated IL-10 was also associated with detectable HCV RNA alone (5.51; 1.17, 25.84).
Detectable HIV and HCV replication versus undetectable replication was associated with inflammatory burden and certain inflammatory biomarkers independently of alcohol consumption, liver fibrosis and other comorbidities.
"Recent studies have demonstrated conflicting results on the levels of Thl and Th2 cytokines in HCV infections (10-14). While some reports have demonstrated elevated levels of IL-2, IFN-gamma (11, 15), IL-4 and IL-10 (14, 16), others have reported no increase in the levels of Thl (13, 17) and/or Th2 cytokines (15). Viral Therapy may be regulating an activated T-cell response in HCV infected patients and this creates a decreased viral load (11). "
[Show abstract][Hide abstract] ABSTRACT: T-helper (Th) lymphocyte cytokine production may be important in the immune pathogenesis of hepatitis C virus (HCV) infections. Th1 cytokines such as; interleukin-2 (IL-2), and interferon gamma (IFN-gamma) are necessary for host antiviral immune responses, while Th2 cytokines (IL-4, IL-10) can inhibit the development of these effector mechanisms.
The aim of the present study was to assess the serum profile of Th1 and Th2 cytokines in treated and non-treated HCV infected individuals.
This study was carried out in 63 HCV infected patients (31 under treatment and 32 untreated) and 32 matched HCV-sero negative healthy subjects. Serum samples were checked with an enzyme-linked immune sorbent assay (ELISA) for IL-2, IL-4, IL-10 and IFN-gamma.
Levels of circulating IL-2, IL-4, IL-10 and IFN-gamma were significantly elevated in HCV patients versus normal controls (2 822.6 ± 1 259.92 vs. 950.8 ± 286.9 pg/mL; 1 987 ± 900.69 vs. 895.91 ± 332.33 pg/mL; 1 688.5 ± 1 405.1 vs. 519.03 ± 177.64 pg/mL and 1 501.9 ± 1 298 vs. 264.66 ± 71.59 pg/mL, respectively; P < 0.001). The serum levels of all cytokines were significantly lower in the patients under treatment than those of the untreated patients (P < 0.001).
On the basis of our data, the simultaneous increase of Th1 and Th2 related cytokines may indicate that both Thl and Th2 cytokines are involved in the pathogenesis of HCV infections. Moreover, this activated T-cell response in HCV infected patients may be regulated by treatment.
[Show abstract][Hide abstract] ABSTRACT: Interferon-alpha-based treatment is a standard therapy to cure hepatitis C virus-infected patients. However, the reasons for the failure of interferon-alpha treatment in some patients have not been fully elucidated. We evaluated the differences in the expression levels of various cytokines among patients with and without sustained viral response (SVR). We found that the chemokines (MIG and IP-10) and inflammation-related cytokines (IL-6) were transiently elevated in patients with SVR(+) before interferon-alpha treatment and in the early phase of treatment (week 2), indicating that these cytokines may be related to viral clearance. Furthermore, higher serum levels of Th1 and Th2 cytokines (IL-2, IL-4, IL-5, IL-10, tumor necrosis factor, and IFN-gamma) were observed in SVR(-) than in SVR(+) patients, indicating that they may be associated with ineffective anti-HCV immune response. Our data revealed that the patterns of cytokines varied greatly between SVR(+) and SVR(-) patients before and after IFN-alpha treatment.
Biochemical and Biophysical Research Communications 02/2009; 379(4):855-60. DOI:10.1016/j.bbrc.2008.12.114 · 2.30 Impact Factor
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