Relationship between vitamin D and IL-23, IL-17 and macrophage chemoattractant protein-1 as markers of fibrosis in hepatitis C virus Egyptians

World J Hepatol 2012 August 27; 4(8): 242-247

World J Hepatol. 2012 August 27; 4(8): 242-247.
Published online 2012 August 27. doi: 10.4254/wjh.v4.i8.242.


Relationship between vitamin D and IL-23, IL-17 and macrophage chemoattractant protein-1 as markers of fibrosis in hepatitis C virus Egyptians

Noha M El Husseiny, Hala M Fahmy, Waleed A Mohamed and Hisham H Amin.
Noha M El Husseiny, Hala M Fahmy, Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo 11111, Egypt
Waleed A Mohamed, Department of Chemistry, Cairo University, Cairo 12534, Egypt
Hisham H Amin, Clinical Pathology Department, Faculty of Medicine AL Azhar University, Cairo 15533, Egypt

Author contributions: El Husseiny NM did the statistics and wrote the manuscript; Mohamed WA put the idea of the research, collected the data and did the laboratory work; Fahmy HM participated in the idea of the research and participated in writing the manuscript; Amin HH participated in the laboratory work and data collection.

Correspondence to: Noha M El Husseiny, MD, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11111, Egypt. dr_noha2002@yahoo.com
Telephone: +20-100-6803571 Fax: +20-223-667260
Received January 1, 2012; Revised August 6, 2012; Accepted August 23, 2012;

 

 

Discussion Only

 

 Full Text available at WJH World Journal Of Hepatology

 

The liver plays a central role in vitamin D metabolism. Vitamin D inadequacy is common in non-cholestatic chronic liver diseases and correlates with disease severity. The current study showed a significant reduction of vitamin D and its active metabolites in HCV genotype 4-infected patients compared to healthy controls. This reduction was more prevalent and severe in cirrhotic vs non-cirrhotic patients. This is consistent with previous studies done on patients with genotype 1, which showed that vitamin D deficiency is universal (92%) among patients with chronic liver disease, and at least one-third of the patients have severe vitamin D deficiency[^14-16].

 

Our results showed that IL-23 and -17 were markedly increased in HCV-infected patients in comparison to controls. Regulation of Th1 and Th17 responses in HCV-infected individuals was studied, and it was reported that TGF-β and IL-6 promote differentiation of naive murine CD4⁺ T cells into IL-17-secreting Th17 cells. In addition, it has been reported that other innate cytokines, including IL-1, IL-23, TNF-α, and IL-21, in different combinations or with TGF-β, are also involved in differentiation, amplification, or stabilization of the Th17 phenotype[^17,18].

 

Our study reported that there is a significant negative correlation between vitamin D and IL-17 and -23. Previous studies on mice showed that vitamin D is a strong inhibitor of Th17 polarization and Th17 cytokine expression of splenic CD4+ T cells. Furthermore, Th17 differentiation from naïve T cells was affected by vitamin D. These data implicate a regulatory mechanism on Th17 cells by vitamin D, through the reduction of RORgt expression[¹⁹].

 

The effect of vitamin D on the behavior of Th17 cells was investigated in different diseases and it was found that vitamin D suppressed the expression of IL-17 and -23[^20-23].

 

We reported a positive correlation between IL-23 and -17 with viral load, a finding which further support our suggestion regarding the link between vitamin D and both IL-17 and -23 in immune regulation in HCV genotype IV-related chronic liver disease. These findings may support our suggestion that increased IL-17 and -23 could be, at least in part, involved in the role of vitamin D in the immune response in HCV genotype IV-related liver disease and explain how vitamin D deficiency plays a role in increasing liver fibrosis.

 

Our results revealed HCV-infected males and females had no differences with respect to vitamin D levels. In contrast with our results, Arteh et al[²⁴] who reported that African American females with chronic liver disease are at higher risk of vitamin D deficiency.

Our study showed that the viral load mean value was 1.28 × 10⁵ ± 28 × 10³ IU/mL. A significant negative correlation was reported between vitamin D and active vitamin D and viral load (P = 0.0001 and P = 0.001, respectively).

 

Vitamin D is an important immune modulator and preliminary data indicated an association between vitamin D deficiency and SVR rates in HCV as reduced 25-hydroxyvitamin D levels and CYPB27-1260 promotor polymorphism with reduced 1,25-dihydroxyvitamin D levels are associated with failure to achieve SVR in HCV genotypes 1-, 2-, and 3-infected patients[^9,25]. Our HCV patients with genotype IV need further follow up to confirm the effect of vitamin D deficiency on their responses to treatment.

 

There was a significant increase in level of MCP-1 in our patients with all grades of hepatic affection in comparison to controls. Similar results were reported by Camps et al[²⁶]. However, Panasiuk et al[²⁷] reported a decrease in the MCP-1 level in liver cirrhosis in comparison to the controls and did not reflect any inflammatory process in liver cirrhosis. More studies are needed to explore this point of controversy.

 

Our results also revealed a significant negative correlation between vitamin D and MCP-1. This supports the role of decreased vitamin D in inflammation and fibrosis. No previous work in hepatic patients studied this relationship. However, Zehnder et al[²⁸] reported that reduction of the vitamin D hormonal system in kidney disease was associated with increased renal inflammation and fibrosis. Zehnder et al[²⁸] reported a significant negative correlation between vitamin D and MCP-1. Logistic regression analysis with urinary MCP-1 as a binary outcome showed that a 10-unit increase in serum 1,25(OH)₂D or 25OHD resulted in lower renal inflammation[²⁸].

 

On classifying HCV-infected patients according to sonar finding into four groups, vitamin D and active vitamin D were shown to be lower in cirrhotic patients and much lower in patients with HCC, and this difference was highly significant (P = 0.0001). IL-17 and -23 and MCP-1 were higher in advanced liver disease) and the differences were highly significant (P = 0.0001). These findings are concomitant with previous results which indicate that vitamin D inadequacy is common in non-cholestatic chronic liver diseases and correlates with disease severity[¹⁴]. The difference in viral load among these groups may explain in part the difference in levels of inflammatory cytokines.

 

In conclusion, vitamin D deficiency is prevalent in HCV genotype IV-infected patients and viral load is negatively correlated to vitamin D. Whether or not this deficiency is related to HCV-induced chronic liver disease or predisposing factor for higher viral load is a matter of debate. In view of the immune function of vitamin D, vitamin D status may be assessed and supplements may be considered to achieve a SVR with IFN-based therapy. The negative correlation between vitamin D and IL-23 and -17 and MCP-1 may highlight, at least in part, how these cytokines might be involved with vitamin D in immune responses in HCV genotype IV-related liver disease and may explain how vitamin D deficiency plays a role in increasing liver fibrosis.

 

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