IL23/IL-17 serum levels and peg response, vitd3 most powerful il17 suppressor

[stef2011]

DOI: 10.1111 / liv.12701

This article is protected by copyright. All rights reserved.

1 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, The First Affiliated Hospital, School of Medicine
2 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases
3 Department of Radiation Oncology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China

* Corresponding to: Lanjuan Li, MD
State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China.
E-mail: [Email protected]

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record Please cite this article as doi:. 10.1111 / liv.12701


Abstract
Background & Aims

This study investigated the possible use of interleukin (IL) -23 and IL-17 serum levels as indicators for anti-hepatitis B virus (HBV) therapy.
Methods

A total of 127 patients with chronic hepatitis B (CHB) who received pegylated interferon (PegIFN) therapy, 20 chronic asymptomatic HBV carriers (AsCs) and 32 healthy controls were recruited. The serum levels of IL-23 and IL-17 were detected by ELISA. The predictive value of baseline and early on-treatment changes in the levels of IL-23 and IL-17 for therapeutic response were evaluated by receiver-operating characteristic analysis. Multivariate logistic regression models were generated to identify independent factors that affect the clearance of hepatitis B e antigen (HBeAg) and the decline in hepatitis B surface antigen (HBsAg).
Results

The baseline serum levels of IL-23 and IL-17 were higher in patients with CHB than in normal controls and in AsCs. High levels of pre-treatment IL-23 and IL-17 and more significant on-treatment reductions in IL-23 and IL-17 levels were observed in patients with CHB who achieved HBeAg clearance or a decline in HBsAg> 1 log10 IU / mL compared with patients who were persistently HBeAg-positive or who experienced a decline in HBsAg <1 log10 IU / mL. The predictive cut-off value of IL-23 for HBeAg clearance was 135 pg / mL, and the specificity and sensitivity were 71.4% and 70%, respectively. A high pre-treatment level of IL-23 was an independent factor for the prediction of the therapeutic response in patients with HBeAg-positive CHB. Early on-treatment changes of IL-23 and IL-17 showed no predictive value.
Conclusions

A high pre-treatment serum IL-23 level predicts the therapeutic response in HBeAg-positive CHB patients during PegIFN therapy.

This article is protected by copyright. All rights reserved.

[stef2011]

http://www.ncbi.nlm.nih.gov/pubmed/24451309

Association between serum 25-hydroxyvitamin D and inflammatory cytokines in healthy adults.
Sun X1, Cao ZB2, Zhang Y3, Ishimi Y4, Tabata I5, Higuchi M6.
Author information
Abstract
Here, we aimed to examine the associations between levels of serum 25-hydroxyvitamin D [25(OH)D] and inflammatory cytokines in healthy Japanese adults. A total of 95 healthy adults (61 women; age range 21-69 years) participated in our study. Fasting blood samples were analyzed for 25(OH)D, 1,25-dihydroxyvitamin D [1,25(OH)2D], interferon-γ (IFN-γ), interleukin-6 (IL-6), and interleukin-17 (IL-17) levels using enzyme-linked immunosorbent assays kits. Total percent body fat was determined by dual energy X-ray absorptiometry (DXA). Moderate to vigorous physical activity (MVPA) was assessed objectively using an activity monitor for 7 days. The mean 25(OH)D concentration was 34.7 nmol/L, and 83 subjects had 25(OH)D concentrations less than 50 nmol/L. Multiple linear regression analysis revealed that serum 25(OH)D level was positively related to plasma IL-17 level (β=0.26, p=0.025), after adjustment for gender, age, vitamin D intake, alcohol consumption, smoking status, and percent body fat. This relationship remained statistically significant (β=0.28, p=0.019) even after additional adjustment for MVPA. However, no significant association was found between serum 25(OH)D level and plasma IFN-γ or IL-6 levels. In conclusion, this study identified a high prevalence of vitamin D deficiency in healthy Japanese adults. Serum 25(OH)D level was positively related to IL-17 level, independent of physical activity.

[stef2011]

extremely interesting, interplay of vitD25oh, vitd1.25, hcvrna, IL17 and IL23 in hcv chronic infection

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406428/

Vitamin D deficiency: Correlation to interleukin-17, interleukin-23 and PIIINP in hepatitis C virus genotype 4
Mona F Schaalan, Waleed A Mohamed, and Hesham H Amin
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Abstract
AIM: To assess vitamin D (Vit D) abnormalities in hepatitis C infected patients and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide of type III pro-collagen (PIIINP) as immune response mediators.

METHODS: The study was conducted on 50 Egyptian patients (36 male, 14 female) with hepatitis C virus (HCV) infection, who visited the Hepatology Outpatient Clinic in the Endemic Disease Hospital at Cairo University. Patients were compared with 25 age- and sex-matched healthy individuals. Inclusion criteria were based on a history of liver disease with HCV genotype 4 (HCV-4) infection (as new patients or under follow-up). Based on ultrasonography, patients were classified into four subgroups; 14 with bright hepatomegaly; 11 with perihepatic fibrosis; 11 with hepatic cirrhosis; and 14 with cirrhosis and hepatocellular carcinoma (HCC). Total Vit D (i.e., 25-OH-Vit D) and active Vit D [i.e., 1,25-(OH)2-Vit D] assays were carried out using commercial kits. IL-17, IL-23 and PIIINP levels were assayed using enzyme linked immunosorbent assay kits, while HCV virus was measured by quantitative and qualitative polymerase chain reaction.

RESULTS: Levels of Vit D and its active form were significantly lower in advanced liver disease (hepatic cirrhosis and/or carcinoma) patients, compared to those with bright hepatomegaly and perihepatic fibrosis. IL-17, IL-23 and PIIINP levels were markedly increased in HCV patients and correlated with the progression of hepatic damage. The decrease in Vit D and active Vit D was concomitant with an increase in viral load, as well as levels of IL-17, IL-23 and PIIINP among all subgroups of HCV-infected patients, compared to normal healthy controls. A significant negative correlation was evident between active Vit D and each of IL-17, IL-23 and PIIINP (r = -0.679, -0.801 and -0.920 at P < 0.001, respectively). HCV-infected men and women showed no differences with respect to Vit D levels. The viral load was negatively correlated with Vit D and active Vit D (r = -0.084 and -0.846 at P < 0.001, respectively), and positively correlated with IL-17, IL-23 and PIIINP (r = 0.951, 0.922 and 0.94 at P < 0.001, respectively). Whether the deficiency in Vit D was related to HCV-induced chronic liver disease or was a predisposing factor for a higher viral load remains to be elucidated.

CONCLUSION: The negative correlations between Vit D and IL-17, IL-23 and PIIINP highlight their involvement in the immune response in patients with HCV-4-related liver diseases in Egypt.

[stef2011]

Vitamin D suppresses Th17 cytokine production by inducing C/EBP homologous protein (CHOP) expression.

Seon Hee Chang
Seon Hee Chang
Yeonseok Chung
Yeonseok Chung
Chen Dong
Chen Dong
Department of Immunology, The University of Texas, MD Anderson Cancer Center, Houston, Texas 77054, USA.
Journal of Biological Chemistry (Impact Factor: 4.65). 10/2010; 285(50):38751-5. DOI: 10.1074/jbc.C110.185777
Source: PubMed
ABSTRACT Vitamin D has been shown to have immunomodulatory function, but the molecular basis for it has not been well understood. In this study, we found that vitamin D receptor expression was induced in a CD4+ effector T cell lineage, Th17 cells, which required the transcription factors, RORα, RORγt, and STAT3. Treatment of mice with an active ligand of vitamin D receptor (VDR), 1,25-dihydroxyvitamin D(3) (1,25D3), ameliorated experimental autoimmune encephalomyelitis, accompanied with reduced IL-17 and IL-17F expression. In vitro, treatment of CD4+ T cells with the physiological doses of 1,25D3 preferentially inhibited cytokine production by Th17 cells, in a VDR-dependent manner, without affecting the expression of transcription factors or surface molecules. Moreover, at these concentrations, cytokine expression was suppressed only at protein but not at mRNA levels. Stimulation of Th17 cells with 1,25D3, in a concentration-dependent manner, induced the expression of C/EBP homologous protein (CHOP), a molecule involved in endoplasmic reticulum stress and translational inhibition. In addition, overexpression of CHOP in developing Th17 cells suppressed their cytokine production. Our results suggest a novel, post-transcriptional mechanism whereby Th17 cytokines are inhibited by VDR, which may underscore future therapeutic usage of vitamin D in treatment of autoimmune diseases.