In vivo preliminary study of acute and chronic pharmacodynamics of JAK inhibitors baricitinib for alopecia areata
Objective To evaluate the efficacy of baricitinib in mice with alopecia areata and to provide a reference for preclinical in vivo pharmacodynamics of related JAK inhibitors.Methods Acute pharmacodynamic model was established by administering a single intraperitoneal injection of the alopecia areata-associated inflammatory factor interleukin 2(IL-2)to BALB/c mice.The serum interferon-gamma(IFN-γ)levels were assayed to rapidly evaluate the anti-inflammation activity of baricitinib in vivo.The alopecia areata models induced by imiquimod in C3H/HeJ mice were established.The alopecia areata severity scores,splenic index,pathological staining of tissue and changes in infiltrating inflammatory cells in each group were compared to determine the therapeutic effect of baricitinib on alopecia areata in mice.Results Compared with the model group,baricitinib inhibited serum IFN-γ production in a dose-dependent manner;imiquimod induced severe alopecia areata in C3H/HeJ mice,while baricitinib effectively inhibited the progression of alopecia areata,suppressed systemic inflammation-induced splenomegaly,ameliorated perifollicular CD4+and CD8+T-cell infiltration and promoted the hair follicle growth cycle in mice.Conclusion baricitinib has potent anti-inflammation activity in vivo and may ameliorate the progression of alopecia areata by reducing T-cell infiltration in the skin and promoting the restoration of the hair follicle growth cycle.
alopecia areataJAK inhibitorJAK/STAT signaling pathwayacute/chronic pharmaco-dynamic model
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