The therapeutic efficacy of Tacrolimus in colitis progression and perpetuation is examined by administering it to DSS-treated mice from Days 10 to 16 or 23. Compared to normal mice, DSS-treated control animals at Days 17 and 24 exhibit significantly shortened colon length and higher colon weight. Additionally, colon weight per unit length is over double that of normal mice. Both 7 and 14-day Tacrolimus treatments significantly suppress increases in colon weight per unit length in DSS-treated animals compared to controls. However, Tacrolimus does not restore colon shortening. Moreover, the inhibitory effect of Tacrolimus on colon weight per unit length increase is more pronounced with 14-day treatment compared to 7-day treatment, as indicated by inhibitory percentages (59% vs. 28%) ^[4].

Tacrolimus (FK506) inhibits calcium-dependent processes, including IL-2 gene transcription, NO synthase activation, cell degranulation, and apoptosis. It also enhances glucocorticoid and progesterone actions by binding to FKBPs within the hormone receptor complex, preventing degradation. Additionally, Tacrolimus may upregulate TGFβ-1 gene expression similar to CsA. T cell proliferation in response to T cell receptor ligation is inhibited by Tacrolimus ^[1].

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