The disease of FIP is predominantly immune-mediated. Lesions are distributed along the vasculature, particularly along veins.15 Emigration of infected monocytes/macrophages from blood vessels into perivascular regions incites local inflammatory responses.
Type II and type III hypersensitivity responses occur, with complement activation and cellular destruction. This destruction
may occur widely throughout an infected cat's tissues, leading to increased vascular permeability, extensive pyogranulomatous
lesions, and the classic signs of the effusive, or wet, form of FIP. Alternatively, focal lesions may be confined to one or
more organ systems in the noneffusive, or dry, form of FIP.
The cells involved in the inflammatory process are primarily macrophages and neutrophils; however, B lymphocytes play a critical
role in producing disease.16 In cats that develop FIP, a strong humoral response to infection occurs, with inadequate cell-mediated response by cytotoxic
T cells.17 This antibody production is ineffective in clearing the virus and contributes to the immune-mediated disease.18
Potential causes of immune-mediated effects
The factors responsible for the unsuccessful immune response described above are unknown. Various mechanisms appear to be
Cytokines. A great deal of work has centered on cytokine responses in affected cats. Unfortunately, here, too, the results are not
consistent. Much focus has been placed on interferon gamma because of its role in enhancing the cell-mediated immune response.
While serum interferon gamma concentrations were not found to differ between cats with FIP and healthy cats with feline coronavirus
in catteries with a low prevalence of FIP, higher serum interferon gamma concentrations were seen in healthy cats with feline
coronavirus as compared with cats with FIP in catteries with a high prevalence of FIP.19 In addition, interferon gamma concentrations were significantly higher in the effusions than in the serum of cats with FIP,
indicating that, at least at the tissue level, cell-mediated immunity may contribute to lesion development.19 In particular, it indicates that local activation of macrophages by interferon gamma may be occurring, leading to enhanced
viral replication.20 In contrast, a systemic increase in interferon gamma concentrations, as indicated by elevated expression in blood, may protect
infected cats from disease.19,21
Other studies have examined the expression of various cytokines in blood, tissue, or both, often comparing cytokine production
between cats with FIP and healthy cats with feline coronavirus. Tumor necrosis factor alpha (TNF-alpha) expression increases
in infected macrophages and may increase expression of the receptor for feline coronavirus on macrophages, enhancing viral
replication.22 Interleukin-10 and interleukin-12 concentrations have been shown to be lower in cats with FIP as compared with healthy cats
with feline coronavirus infection.10 The decreased levels of these cytokines may lead to excessive macrophage activation and inhibition of the cell-mediated
immune response. While the virus is not cleared, macrophage infection continues, also leading to activation. These activated
monocytes/macrophages adhere to vascular endothelium and infiltrate the perivascular region, causing vasculitis and secreting
pro-inflammatory cytokines, a key contributor to the pathology associated with FIP.15,23
T lymphocyte depletion. Another finding in cats with FIP is lymphocyte depletion, particularly of T lymphocytes,24 through apoptosis. The virus does not replicate in lymphocytes, so some other mechanism must be responsible for this process.
The resultant depletion of T lymphocytes contributes to enhanced viral replication, as these cells are important in cell-mediated
immunity. Soluble mediators released from infected monocytes and macrophages may be responsible for this phenomenon. In particular,
TNF-alpha may lead to apoptosis, primarily of CD8+ T cells, the cytotoxic T cells, which are critical to cell-mediated immunity.22 At least one group of investigators propose that the virus-driven T cell depletion occurring in infected cats that do not
mount a quick and effective cell-mediated immune response leads to loss of immune control and unchecked viral replication.12
Genetic and environmental factors. The ability of an animal to mount an effective immune response may lie at least in part in its genetic make-up. Studies have
shown a genetic predisposition to disease occurrence. Certain breeds, including Bengals, Birmans, and Himalayans, are more
likely to develop FIP.25 In addition, susceptibility along familial lines has also been documented.26 It is not known what specific host genetic factor or factors may be involved, but these factors may include major histocompatibility
complex haplotype or T lymphocyte receptors.27
Environmental factors may also play a role. Stressors, such as crowded housing, trauma, surgery (e.g. ovariohysterectomy, orchiectomy), or other conditions, may precipitate FIP development.28 It has been shown that concurrent infection with other agents, particularly the feline retroviruses, also predisposes cats
to develop FIP, probably through immunosuppression.