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Nutritional Immunology

Biotin Status Affects Nickel Allergy via Regulation of Interleukin-1β Production in Mice^1,2

³ Division of Oral Immunology, Department of Oral Biology, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan ⁴ Division of Orthodontics and Dentofacial Orthopedics, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan ⁵ Division of Fixed Prosthodontics, Department of Restorative Dentistry, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan ⁶ Division of Cell Biology, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan

Biotin, a water-soluble B complex vitamin, is possibly involved in chronic inflammatory diseases, although the detailed mechanisms are unclear. In this study, we investigated the effects of biotin status on nickel (Ni) allergy in mice. Mice were fed a basal or biotin-deficient (BD) diet for 8 wk and sensitized with an intraperitoneal injection of NiCl₂ and lipopolysaccharide. Ten days after sensitization, NiCl₂ was intradermally injected into pinnas and ear swelling was measured. For in vitro analysis, we cultured a murine macrophage cell line, J774.1, under a biotin-sufficient (C, meaning control) or BD condition for 4 wk and analyzed interleukin (IL)-1 production. Significantly higher ear swelling was induced in BD mice than C mice. Adaptive transfer of splenocytes from both C and BD mice induced Ni allergy in unsensitized mice. Regardless of donor mice, ear swelling was significantly higher in BD recipient mice than C recipient mice. Ni allergy was not induced in either C or BD IL-1^–/– mice. Splenocytes from BD mice produced a significantly higher amount of IL-1β than those from C mice. Production and mRNA expression of IL-1β were significantly higher in BD J774.1 cells than in C cells. Biotin supplementation inhibited the augmentation of IL-1β production in vitro. In vivo supplementation of biotin in drinking water dose-dependently decreased ear swelling in C and BD mice. These results indicate that biotin status affects Ni allergy in the elicitation phase via the upregulation of IL-1β production in mice, suggesting that biotin supplementation may have therapeutic effects on human metal allergy.

^* To whom correspondence should be addressed. E-mail: kuroishi{at}mail.tains.tohoku.ac.jp.

Manuscript received 5 August 2008. Initial review completed 16 September 2008. Revision accepted 7 February 2009.