The T1 endotype was significantly more common in females, and the presence of pus was significantly associated with T3 endotype in all patients with CRS.
Overall, our results highlight the importance of FcγRIIIa-dependent IFN-γ release in preclinical cytokine release assay for the prediction of CRS risk associated with therapeutic IgG1 antibodies.
Taken together, our results suggest that IFN-γ can induce the EMT in nasal epithelial cells, and thus blocking the p38 and ERK pathways could be an effective therapeutic strategy against neutrophil-dominant CRS.
Cytokine release syndrome (CRS) is a potentially severe systemic toxicity seen after adoptive T-cell therapy and caused by T-cell activation and proliferation and is associated with elevated circulating levels of cytokines such as C-reactive protein, interleukin-6 (IL-6), and interferon-γ and has previously been described as a systemic response in hematologic malignancies.
ex vivo VCAM expression was lowest in controls, higher in CRSsNP, and highest in CRSwNP. in vitro stimulation with TNF-α and IL-4, but not IFN-γ, increased VCAM among CRSsNP, while expression in CRSwNP remained elevated with all treatments except IFN-γ. ex vivo ICAM expression was elevated in both CRS subtypes. in vitro stimulation with TNF-α and IFN-γ, but not IL-4, increased ICAM expression in all patients with the largest effects among the CRSsNP subgroup.
The disruption of epithelial integrity by IFN-γ and IL-4 in vitro indicates a possible role for these proinflammatory cytokines in the pathogenesis of patients with CRS.