Endocrinol Metab.  2018 Jun;33(2):296-304. 10.3803/EnM.2018.33.2.296.

Influence of Vitamin D Deficiency on Progression of Experimental Otitis Media in Rats

Affiliations
  • 1Department of Otorhinolaryngology-Head and Neck Surgery, BK21plus, Korea University College of Medicine, Seoul, Korea.
  • 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea. hschoi402@dumc.or.kr
  • 3Department of Otorhinolaryngology-Head and Neck Surgery, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea. cho69@dumc.or.kr

Abstract

BACKGROUND
Vitamin D plays an important role in the immune response against infection. The purpose of the present study was to investigate the influence of vitamin D deficiency on the progression of otitis media (OM) using an experimental rat model.
METHODS
Four-week-old male Sprague-Dawley rats (n=72) were divided into two groups based on their diet: a control diet group (n=36) and a vitamin D-deficient diet group (n=36). After 8 weeks of diet, experimental OM was induced by inoculation of non-typeable Haemophilus influenzae in the middle ear cavity. The rats were evaluated with otomicroscopy to determine the inflammation in the middle ear mucosa on days 1, 2, 4, 7, and 14 post-inoculation. Bullae from sacrificed rats were collected and analyzed histologically.
RESULTS
The middle ear mucosa from rats with vitamin D deficiency showed a significantly higher thickness than that of controls during the course of OM. The maximum mucosal thickness was 56.0±9.1 µm in the vitamin D deficiency group, and 43.9±9.8 µm in the control group, although there was no significant difference in the tympanic membrane score between the two groups evaluated with otomicroscopy. An immunohistochemical study showed increased expression of interleukin 6 (IL-6) and tumor necrosis factor α in rats manifesting vitamin D deficiency and decreased expression of IL-10 compared with controls.
CONCLUSION
Our results showed that vitamin D deficiency may exacerbate the pathophysiological changes of OM via altered cytokine production. Therefore, maintaining vitamin D status in the optimal range may be beneficial for proper management of OM.

Keyword

Vitamin D; Infection; Vitamin D deficiency; Otitis media; Rats

MeSH Terms

Animals
Diet
Ear, Middle
Haemophilus influenzae
Humans
Inflammation
Interleukin-10
Interleukin-6
Male
Models, Animal
Mucous Membrane
Otitis Media*
Otitis*
Rats*
Rats, Sprague-Dawley
Tumor Necrosis Factor-alpha
Tympanic Membrane
Vitamin D Deficiency*
Vitamin D*
Vitamins*
Interleukin-10
Interleukin-6
Tumor Necrosis Factor-alpha
Vitamin D
Vitamins

Figure

  • Fig. 1 (A) Serial otomicroscopic images of middle ear in bacterially induced otitis media were taken for 14 days (×90 magnification). (B) The mean value of the tympanic membrane scores in the control group and vitamin D deficiency group (0: normal; 1: 1/2 or less exudate; congestion; 2: more than 1/2 exudate, severe congestion; 3: high-pitched whole effervescent fluid, severe congestion).

  • Fig. 2 (A) H&E stain of middle ear mucosa (×200 magnification). (B) Middle ear mucosa thickness. aP<0.005.

  • Fig. 3 Serum 25-hydroxyvitamin D (25(OH)D) levels in the control group and the vitamin D deficiency group. aP<0.05.

  • Fig. 4 Immunohistochemical stain and the average detection area (%) of (A, B) interleukin 6 (IL-6), (C, D) tumor necrosis factor α (TNF-α), and (E, F) IL-10 for bacterially induced middle ear mucosa. aP<0.05; bP<0.005.


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