Feline infectious peritonitis (FIP) continues to be a significant disease in domestic cats. The pathogenesis of FIP is complex, involving feline coronavirus (FCoV) and an inappropriate humoral response to the virus. Only a minority of FCoV-infected cats develop the lethal disease, and genetic factors are known to play a role in disease development.

Virus factors are important to disease development, as virus strains vary in virulence. It has been theorized that a viral mutation is responsible for the change in biotype of the virus leading to disease production. Speculation on the genomic locale of this mutation has involved the gene encoding the spike protein, as well as genes encoding several nonstructural proteins including 3c, 7a, and 7b. However, no consistent genetic difference between virulent and avirulent biotypes has been found. In fact, a recent study found 100% homology between the enteric and non-enteric viral genome from a cat with FIP. There do appear to be quantitative differences in viral RNA levels in the blood of cats with and without FIP. Rising amounts of viral RNA in the blood seen in end-stage disease may indicate that loss of immune control leads to enhanced viral replication and disease progression. This increased viral replicative capacity may be a key element of FIP pathogenesis.

The lesions associated with FIP are due primarily to immune-mediated destruction. Type II and III hypersensitivity reactions are involved, with immune complex formation, activation of complement, and cytotoxicity of infected macrophages releasing inflammatory mediators. Neutrophils also are attracted to the lesions and release inflammatory mediators as well as cytotoxic factors. Resultant lesions are associated with the vasculature, especially at serosal surfaces, with increased vascular permeability and pyogranulomatous changes.

Susceptibility to disease following FCoV infection appears to be inherited, with breed and familial predisposition. The host genetic factors that lead to increased susceptibility are not clear, but seem to involve the immune response to FCoV infection, in particular, a shift from T helper lymphocyte type I (Th1) to Th type 2 (Th2) response to the infection. The former are important in coordinating cell-mediated immunity, which is protective against FIP, while the latter are important in humoral response. This shift results in an exaggerated humoral response which is not protective, and in fact actually enhances the disease progression as it enhances monocyte/macrophage virus infection and mediates the immunopathology. Since lymphocytes are not target cells of FCoV, it is theorized that secreted factors, including cytokines are critical to the lymphocyte effects, such as the Th2 response and T lymphocyte depletion. In fact, the T lymphocyte response appears to be the decisive factor in disease progression.

Cytokines are important mediators of the immune response. Monocytes and macrophages are major cytokine producers, and are also the target of FIPV infection. T helper lymphocytes are the other major cytokine producer, and determine in large part whether the cell-mediated (via Th1) or humoral (via Th2) arm of the immune response dominates. The cytokine secretion patterns from these cells thus determine the magnitude and direction of the immune response. Cytokines associated with cell-mediated immunity, such as IL-10 and -12, and IFN -γ have been found to decrease in cats that develop FIP. Elevations in cytokines IL-1β and IL-6 have also been found in affected cats which may contribute to the humoral response. An increase in TNF-α has been observed in some studies, and may contribute to the T lymphocyte apoptosis. A recent study has shown that FCoV-infected macrophages produce factors that promote B cell differentiation into plasma cells. This may contribute the exaggerated humoral response.