What are the specific mechanisms of action of Milizumab in treatment?

Milikizumab (Mirikizumab) is a humanized IgG4 monoclonal antibody. Its therapeutic mechanism mainly targets and inhibits the p19 subunit of interleukin-23 (IL-23). This mechanism is highly targeted and effective in modern immunological treatments, especially in the treatment of inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease. IL-23 is a key pro-inflammatory cytokine that regulates the activation, expansion and differentiation of immune cells in the body, especially playing a central role in the maintenance and expansion of Th17 cells. Th17 cells are believed to play a pro-inflammatory role in a variety of autoimmune and inflammatory diseases. The cytokines they produce, such as IL-17 and IL-22, can induce tissue damage, epithelial barrier destruction, and persistent chronic inflammation.

Milizumab selectively inhibitsIL-23 without affecting IL-12. This is very critical because IL-12 is involved in anti-viral and anti-tumor innate immune functions, and its protective role cannot be suppressed at will. Compared with early combined treatment strategies targeting IL-12/IL-23 (such as ustekinumab), the high selectivity of militizumab achieves a better balance between efficacy and safety. This highly precise method of target inhibition means that militizumab can effectively alleviate the pathological inflammatory process and reduce disease activity while maintaining some immune functions.

At the molecular level, milizumab bindsto the p19 subunit of IL-23 and prevents it from binding to the IL-23R receptor, thereby interrupting the downstream JAK-STAT signaling pathway. Activation of this pathway can trigger the expression of a variety of pro-inflammatory genes, thereby amplifying the inflammatory response. By blocking this pathway, militizumab can not only relieve clinical symptoms, such as diarrhea, abdominal pain, and rectal bleeding, but also promote the healing of the intestinal mucosa. It is a biological agent with profound immunomodulatory effects.

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