Tacrolimus and vitamin D both suppress IL-2 production.
The mechanisms of IL-2 suppression is different however. Tacrolimus binds FKBP12 to inhibit calcineurin, blocking NFAT dephosphorylation and IL-2 gene transcription in activated T cells. Vitamin D (1,25(OH)₂D₃) activates VDR to directly inhibit IL-2 promoter. High vitamin D levels correlate with reduced IL-2 and Th1 suppression.
Oral vitamin D are pro-allergic in newborns as I have described in a dozen papers. So if the prohormone vitamin D and the calcineurin inhibitor tacrolimus share the same immunological endpoint IL2, I would anticipate that tacrolimus can make you allergic. And well – only today I discovered that is is true while working on an unrelated review of tacrolimus. So let‘s search the literature https://doi.org/10.1111/j.1365-2222.2011.03761.x says
Results The prevalence of sensitization was significantly higher in the tacrolimus- than in the cyclosporin A-treated group (34%, n = 34, vs. 20%, n = 20; P = 0.026). The rate of clinically relevant allergy in patients receiving tacrolimus was twice that in patients receiving cyclosporin A (15%, n = 15, vs. 8%, n = 8; P = 0.12).
So this study seems to confirm my hypothesis. Let’s look at another study https://doi.org/10.1016/j.aller.2017.09.030
Transplant acquired food allery was found in 7/12 (58%) children with liver transplantations and in none of the 10 children with kidney transplantations.
This study has another interesting observation. Conceptually, the “portal–hepatic immune filter + tacrolimus‑induced Th2 shift + high early antigen load in a young gut” model is consistent with this paper. The kidney, lacking this gut–portal interface and typically being transplanted in older children, sits in a different immunologic context, which likely explains why tacrolimus appears “allergy‑inducing” only in the liver setting rather than via renal blood flow .
