Immune mechanisms in the pathogenesis of feline infectious peritonitis in renal tissue: Focus on lymphocytes and cytokines in effusive and non-effusive forms.

Abstract

Feline infectious peritonitis (FIP) is a fatal systemic disease caused by a virulent biotype of feline coronavirus, characterized by complex and heterogeneous immune responses. This study aimed to comparatively evaluate renal histopathological alterations and immune profiles in effusive and non-effusive forms of FIP, with particular emphasis on cytokine expression, lymphocyte subsets, and apoptosis. Formalin-fixed, paraffin-embedded kidney tissues from 40 cats with immunohistochemically confirmed FIP (20 effusive, 20 non-effusive) were retrospectively analyzed. Renal lesions were semi-quantitatively scored using digital pathology, and immunohistochemistry was performed to assess IL-1, IL-6, TNF-α, CD8, CD19, and Caspase-3 expression. Effusive FIP was characterized by prominent vascular and exudative lesions, accompanied by significantly increased expression of proinflammatory cytokines (IL-1, IL-6, TNF-α) and higher CD19B-cell immunoreactivity, consistent with a cytokine-driven, humoral-dominant immune response. In contrast, non-effusive FIP exhibited more localized granulomatous inflammation, increased CD8T-cell infiltration, more pronounced interstitial fibrosis, and significantly higher Caspase-3 immunoreactivity, indicating enhanced apoptotic activity. Correlation analysis demonstrated no consistent positive association between CD8T-cell density and Caspase-3 expression, suggesting that apoptosis in renal tissue is not solely mediated by cytotoxic T-cell activity. Furthermore, despite elevated TNF-α expression in effusive cases, Caspase-3 immunoreactivity remained relatively low, implying that alternative, potentially caspase-independent mechanisms of cell injury may predominate in this form. Overall, these findings indicate that effusive and non-effusive FIP are associated with distinct patterns of immune polarization and tissue injury rather than representing sequential stages of a uniform pathogenic process. Recognition of these divergent immunopathological profiles may contribute to improved interpretation of FIP lesions and support the development of targeted diagnostic and therapeutic strategies.