Effect of rhAC (recombinant human acid ceramidase) treatment on inflammatory mediator production by cystic fibrosis (CF) and non-CF airway epithelial cell cultures. (A–C) Time course of apical secretion of IL-8 (A), IL-1β (B), and TNFα (C) from CF and non-CF cultures at baseline and after a single treatment with rhAC. (D) Apical secretion of IL-8 from cultures after pretreatment with combinations of ivacaftor, tezacaftor–ivacaftor, and rhAC. (A–C) n = 6 separate experiments; (D) n = 4, all from individual donors. (D) CF group all F508del/F508del genotype. Data are presented as mean ± SD for A–C; for D, individual data points are presented along with the mean (horizontal line) ± SD (error bars). For statistical tests used, see the online supplement. *P < 0.05 and ***P ≤ 0.001. LLOD = lower limit of detection; ns = nonsignificant (P ≥ 0.05); TNF = tumor necrosis factor.