| Summary: | (1) Background: Despite cleft lips and palates belonging to the most common orofacial congenital anomalies, their morphopathogenesis is not yet fully understood. The study aimed to determine the distribution and relation of cytokines interferon-γ (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-2, IL-7, IL-12, and IL-13 in the cleft affected mucosa of the lip. (2) Materials and Methods: Twenty cleft lip (CL) mucosal samples and seven control tissues of oral cavity mucosa were included in the study. Specimen were obtained during reconstruction surgeries and processed by hematoxylin and eosin staining and immunohistochemistry for IFN-γ, TNF-α, IL-2, IL-7, IL-12, and IL-13. (3) Results: The distribution of cytokines was higher overall in the cleft affected epithelium compared to the connective tissue, with TNF-a, IL-2, and IL-12 displaying the highest number of immunopositive cells. With the exception of IL-2, CL specimen showed higher immunoreactivity. IFN-γ displayed only minor immunoreactivity, with no expression in the control epithelium. Correlation analysis was strongest between CL epithelial IL-13 and IFN-γ (z = 0.71, <i>p</i> < 0.0001). (4) Conclusions: The CLP affected epithelium displays high degrees of plasticity in expressing different cytokines, pointing towards the stimulation of a local adaptive immune response based on consistent inflammatory processes.
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