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Co-administration of exogenous protease inhibitors may counteract NE-mediated degradation, enhancing the efficacy of biologic therapy ( 4 The role of macrophages in UC 4.1 The role of M1 macrophages in UC Macrophages exhibit phenotypic plasticity in response to microenvironmental cues, polarizing into pro-inflammatory (M1) or anti-inflammatory (M2) subsets ( Table 1 )