Elevated Pro-inflammatory Cytokine Levels in Acute Reflux Esophagitis Are Reduced by 1,25 Dihydroxy Vitamin D3

1,25-二羟基维生素D3可降低急性反流性食管炎中升高的促炎细胞因子水平

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Abstract

BACKGROUND/AIM: Gastric acid reflux into the esophagus can cause irritation and inflammation of the esophagus and progress to reflux esophagitis (RE). Vitamin D3 (VitD3) has anti-inflammatory effects and plays an important regulatory role in adaptive and innate immunity. We hypothesized that VitD3 may play a protective role in RE. MATERIALS AND METHODS: Seventy male Sprague-Dawley rats were used, and acute RE (n=35) or chronic RE (n=35) were surgically induced. The effects of different doses of VitD3 on morphological changes and alteration of pro-inflammatory cytokine levels were examined in the rat models. Western blot analysis was performed to determine protein expression levels of IL-1β, IL-6, and IL-8 in esophageal tissues. Serum levels of VitD3 and calcium were determined using enzyme-linked immunosorbent assays. RESULTS: The protein expression of pro-inflammatory cytokines IL-1β, IL-6, and IL-8 was found significantly increased in RE. VitD3 treatment significantly reduced the levels of these pro-inflammatory cytokines in both the low-dose and high-dose VitD3 groups compared to control groups in acute RE, but not chronic RE. Macrographic and histopathological examination revealed various degrees of esophageal impairment in rats following surgical induction of acute or chronic RE in rats. These impairments were not improved by VitD3. Morphological grading of esophageal mucosa showed no significant differences between acute and chronic RE. Elevated serum levels of calcium were observed after VitD3 treatment. CONCLUSION: IL-1β, IL-6, and IL-8 levels were significantly elevated in RE. The abnormal increase in these important pro-inflammatory cytokines was suppressed by VitD3 in the rat models of acute RE. These novel findings suggest a potential protective role of VitD3 in early-stage RE.

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