The therapeutic effect of Tacrolimus on the progression and perpetuation of colitis is investigated by administering Tacrolimus to Dextran sulfate sodium (DSS)-treated mice from Days 10 to 16 or to 23. Compared with normal animals, DSS-treated control mice at Days 17 and 24 exhibit significantly shortened colon length and higher colon weight. Additionally, colon weight per unit length in the control group is more than twice that in the normal group. While both 7 and 14-day treatments with Tacrolimus significantly suppress increases in colon weight per unit length in DSS-treated animals compared with the control group, this treatment does not restore colon shortening. Moreover, the inhibitory effect of Tacrolimus on increases in colon weight per unit length is more pronounced with 14-day treatment than with 7-day treatment, as evidenced by the inhibitory percentages (59% vs. 28%) ^[4].

Tacrolimus monohydrate (FK506 monohydrate; Fujimycin monohydrate; FR900506 monohydrate) inhibits calcium-dependent processes, including IL-2 gene transcription, NO synthase activation, cell degranulation, and apoptosis. Additionally, it potentiates the actions of glucocorticoids and progesterone by binding to FKBPs within the hormone receptor complex, preventing degradation. Tacrolimus may also enhance the expression of the TGFβ-1 gene similar to CsA. Moreover, Tacrolimus inhibits T cell proliferation in response to ligation of the T cell receptor ^[1].

Treatment with a low concentration of Tacrolimus (FK506, 10 μg/L) has no significant effect on the proliferation of MH3924A cells (P=0.135). However, higher concentrations of Tacrolimus (100-1,000 μg/L) significantly enhance cell proliferation (P<0.01). AMD3100 at any concentration (10, 50, or 100 μg/L) does not visibly affect MH3924A cell proliferation (P>0.05). Nevertheless, when different concentrations of AMD3100 are combined with 100 μg/L Tacrolimus, the in vitro proliferation of MH3924A cells is increased (P<0.01) ^[3].