Serum Interleukin (IL)-10 and IL-12 Levels and <i>Il28B</i> Gene Polymorphisms: Pretreatment Prediction of Treatment Failure in Chronic Hepatitis C

Umemura, Takeji; Joshita, Satoru; Yoneda, Suguru; Katsuyama, Yoshihiko; Ichijo, Tetsuya; Matsumoto, Akihiro; Yoshizawa, Kaname; Ôta, Masao; Tanaka, Eiji

doi:10.3851/imp1869

Cited by 32 publications

(37 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Second, we observed that blocking IL-12 but not IL-18 abrogates the IL-28B genotype dependent differences in monocyte-induced NK cell activation. Moreover, an association between the IL-28B polymorphism and cytokine levels has been reported before [30–32]. However, blocking of either IL-12 or IL-18 did not completely abrogate differential IFN-g production of NK cells from patients carrying different IL28B genotypes, suggesting that factors other than IL-12/IL-18 also might play a role in this context.…”

Section: Discussionmentioning

confidence: 61%

IL-28B Genetic Variants Determine the Extent of Monocyte-Induced Activation of NK Cells in Hepatitis C

et al. 2016

View full text Add to dashboard Cite

BackgroundImmuno-genetic studies suggest a functional link between NK cells and λ-IFNs. We recently showed that NK cells are negative for the IFN-λ receptor IFN-λR1 and do not respond to IFN-λ, suggesting a rather indirect association between IL-28B genotype and NK cell activity.MethodsA total of 75 HCV(+) patients and 67 healthy controls were enrolled into this study. IL-28B (rs12979860) and IFNL-4 (rs368234815) genotypes were determined by rtPCR. Total PBMC, monocytes, and NK cells were stimulated with IL-29, the TLR-7/8 agonist R848, or a combination of both. NK cell IFN-γ response was analysed by FACS. IL-12 and IL-18 secretion of monocytes was studied by ELISA. In blocking experiments anti-IL-12/anti-IL-18 were used.ResultsFollowing stimulation of total PBMCs with R848 we found NK cell IFN- γ responses to vary with the IL-28B genotype, with carriers of a T/T genotype displaying the lowest frequency of IFN-γ(+)NK cells. When isolated NK cells were studied no such associations were observed, indicating an indirect association between IL-28B genotype and NK cell activity. Accordingly, we found R848-stimulated monocytes of patients with a T/T genotype to be significantly less effective in triggering NK cell IFN- γ production than monocytes from carriers of a non-T/T genotype. In line with these findings we observed monocytes from T/T patients to secrete significantly lower concentrations of IL-12 than monocytes from non-T/T individuals.ConclusionsOur data indicate that monocytes from carriers of an IL-28B T/T genotype display a reduced ability to stimulate NK cell activity and, thus, provide a link between IL-28B genotype and NK functions.

show abstract

Section: Discussionmentioning

confidence: 61%

IL-28B Genetic Variants Determine the Extent of Monocyte-Induced Activation of NK Cells in Hepatitis C

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Genotyping of the rs8099917 SNP was performed using the ABI TaqMan allelic discrimination kit and an ABI 7500 Real Time PCR System (Applied Biosystems) [10].…”

Section: Genotyping Of Il-28 Snp (Rs8099917)mentioning

confidence: 99%

Association of IL28B gene polymorphism with development of hepatocellular carcinoma in Japanese patients with chronic hepatitis C virus infection

et al. 2012

Self Cite

View full text Add to dashboard Cite

IL28B single nucleotide polymorphisms (SNPs) are associated with spontaneous and treatment-induced elimination of hepatitis C virus (HCV). To assess whether the IL28B rs8099917 SNP also affects the progression of chronic HCV infection, we genotyped 511 Japanese HCV patients, including 69 with hepatocellular carcinoma (HCC). The T/T genotype of rs8099917 was not associated with the development of HCC (p = 0.623), although stepwise logistic regression analysis showed that liver cirrhosis, age greater than 68 years, and serum albumin <4.2 mg/dl were associated with HCC onset. It appears that the IL28B SNP does not directly influence hepatocarcinogenesis in chronic HCV infection.

show abstract

“…Umemura et al (2011) who identified a high baseline levels of IL-10 (p<0.001) was significantly associated with a Non-Virological Response (NVR) in their cohort. On the other hand, a 12-month IL-10 therapy in patients with advanced fibrosis led to increased levels of serum HCV RNA and a reduction in fibrosis score suggesting that high levels of IL-10 not only decrease fibrogenesis but also lead to an increased HCV viral burden.…”

Section: Discussionmentioning

confidence: 99%

Factors Affecting the Response to Interferon Alpha Therapy in Egyptian HCV Patients

Alhusseini

Serry²,

Kadry³

et al. 2015

American Journal of Immunology

View full text Add to dashboard Cite

show abstract

Serum Interleukin (IL)-10 and IL-12 Levels and Il28B Gene Polymorphisms: Pretreatment Prediction of Treatment Failure in Chronic Hepatitis C

Cited by 32 publications

References 36 publications

IL-28B Genetic Variants Determine the Extent of Monocyte-Induced Activation of NK Cells in Hepatitis C

IL-28B Genetic Variants Determine the Extent of Monocyte-Induced Activation of NK Cells in Hepatitis C

Association of IL28B gene polymorphism with development of hepatocellular carcinoma in Japanese patients with chronic hepatitis C virus infection

Factors Affecting the Response to Interferon Alpha Therapy in Egyptian HCV Patients

Contact Info

Product

Resources

About