Increased contact hypersensitivity response in mice by topical application of 1 alpha,25-dihydroxyvitamin D3 to elicitation site.

Recent evidence indicates that the biologically active metabolite of vitamin D3, 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], has an effect on the regulation of the immune response. We investigated whether topical treatment of mice with 1 alpha,25(OH)2D3 influences the contact hypersensitivity (CHS) response to trinitrochlorobenzene (TNCB). 1 alpha,25(OH)2D3 was applied to the dorsal trunk of A/J mice on days 0-3, and on day 4 topical application of 5% TNCB on the 1 alpha,25(OH)2D3-treated site was performed. The mice were tested for CHS on day 10 by applying 1% TNCB to the ears. No effect on induction of CHS response to TNCB was observed in 1 alpha,25(OH)2D3-treated mice compared with 24,25-dihydroxyvitamin D3[24,25(OH)2D3]-treated mice as control. In a second experiment, the dorsal trunk of A/J mice was treated with 5% TNCB on day 0. The topical application of 1 alpha,25(OH)2D3 on the ears was performed from days 2 to 5. On day 6, the mice were tested for CHS by applying 1% TNCB to the 1 alpha,25(OH)2D3-treated ears. When 1 alpha,25(OH)2D3 was administered to the elicitation site prior to the challenge, pretreatment of mice with 1 alpha,25(OH)2D3 increased their response to TNCB by 40% compared with 24,25(OH)2D3-treated mice as control (P less than 0.01). There were no findings suggesting that the pretreatment of the challenge site with 1 alpha,25(OH)2D3 induced an irritant dermatitis that was superimposed on a subsequent CHS reaction. The 1 alpha,25(OH)2D3 modulation of CHS response to TNCB in mice suggests that the hormone may play a role in the regulation of the immune response in vivo.