Disseminated intravascular coagulation in experimentally induced feline infectious peritonitis

Disseminated intravascular coagulation was induced in kittens by intraperitoneal inoculation of feline infectious peritonitis virus (FIPV). Kittens seronegative to FIPV survived significantly (P less than 0.05) longer than those seropositive to FIPV. Pyrexia, anemia, icterus, hyperbilirubinemia, and elevated concentrations of liver-specific enzymes were detected in the inoculated cats. Lesions induced included disseminated fibrinonecrotic and pyogranulomatous inflammation, hepatic necrosis, and widespread phlebitis and thrombosis. Localization of FIP viral antigen and immunoglobulin G was demonstrated in foci of heptic necrosis by immunofluorescence miroscopy. Lymphopenia, thrombocytopenia, hyperfibrinogenemia, and increased quantities of fibrin-fibrinogen degradation products were present in cats after the onset of clinical illness. Depression of factor VII, VIII, IX, X, XI, and XII plasma activities and prolongation of prothrombin and partial thromboplastin times also developed in infected cats. The accelerated onset of clinical disease and mortality in seropositive kittens vs seronegative kittens and the association of virus and antibody in multiple foci of hepatic necrosis suggest an immune-mediated component is involved in the pathogenesis of this disease.     

Infection studies in kittens, using feline infectious peritonitis virus propagated in cell culture

The propagation of feline infectious peritonitis virus (NW1-FIPV strain) in cell culture is described. Tissue culture-propagated virus was used to inoculate specific-pathogen-free kittens intraperitoneally, intratracheally, or orally. Intraperitoneal inoculation caused seroconversion and effusive peritonitis in 100% of the kittens. Intratracheal inoculation produced disease in 60% of the kittens, and oral inoculation in only 20%. Seroconversions without production of disease occurred in 10% of the kittens inoculated by either the intratracheal or the oral route. The remainder of the kittens inoculated by the intratracheal (30%) and oral (70%) routes did not develop serum antibodies or disease.     

Virion polypeptide specificity of immune complexes and antibodies in cats inoculated with feline infectious peritonitis virus

Immune complexes purified from sera and ascitic fluids of cats after inoculation with feline infectious peritonitis (FIP) virus contained proteins and proteolytic fragments of the peplomer, nucleocapsid, and envelope polypeptides; in addition, host proteins were demonstrated in the immune complexes. Free (uncomplexed) antibodies against the 3 classes of virion polypeptides were detected and quantitated; the weakest and latest response was directed against the peplomer protein. Immunofluorescence titers showed the best correlation with the antibody response directed against the envelope polypeptides. Differences in reactivity were not found between sera and ascitic fluids from the same animals and between seropositive healthy cats and cats which had died of FIP. Humoral antibody and hypergammaglobulinemia showed a linear correlation, but the wide variation in antiviral titers at a given concentration of gamma-globulin indicated that additional (autoimmune) reactions occur during the pathogenesis of FIP.     

Enhanced platelet reactivity in cats experimentally infected with feline infectious peritonitis virus

Platelet function was evaluated in six specific-pathogen-free cats prior to and following intraperitoneal inoculation with feline infectious peritonitis virus (FIPV). By 4 days post-inoculation, platelet samples from five of six cats responded with irreversible platelet aggregation to threshold concentrations of adenosine diphosphate (ADP). This was accompanied by enhanced platelet 14C-serotonin release (greater than 10%) in two cats. Compared to one of six baseline samples, five of five post-inoculation samples exhibited microaggregate formation in response to 20 microM epinephrine. Enhanced platelet 14C-serotonin release did not accompany these responses. Enhanced platelet responses to ADP and epinephrine were also observed on day 11 post-inoculation and day 16 (when one cat died) or 21 (the end of the study). Platelet 14C-serotonin release in response to 20 microM epinephrine increased markedly in three of five cats on day 21. Enhanced collagen-induced platelet responses were not demonstrated. Although the mechanism for the enhanced platelet responses observed on day 4 was unknown, a direct effect on the virus on platelets, mononuclear inflammatory cells, and endothelial cells must be considered.     

Treatment of cats with feline infectious peritonitis

Feline infectious peritonitis (FIP) infection resulting in clinical signs is invariably fatal despite clinical intervention. As FIP is an immune-mediated disease, treatment is mainly aimed at controlling the immune response triggered by the infection with the feline coronavirus (FCoV). Immune suppressive drugs such as prednisone or cyclophosphamide may slow disease progression but do not produce a cure. In nearly every published case report of attempted therapy for clinical FIP, glucocorticoids have been used; there are, however, no controlled studies that evaluate the effect of glucocorticoids as a therapy for FIP. Some veterinarians prescribe immune modulators to treat cats with FIP with no documented controlled evidence of efficacy. It has been suggested that these agents may benefit infected animals by restoring compromised immune function, thereby allowing the patient to control viral burden and recover from clinical signs. However, a non-specific stimulation of the immune system may be contraindicated as clinical signs develop and progress as a result of an immune-mediated response to the mutated FCoV.     

Effect of interferon or Propionibacterium acnes on the course of experimentally induced feline infectious peritonitis in specific-pathogen-free and random-source cats

Seventy-four cats (52 treated and 22 untreated) were evaluated in efficacy studies of interferon (IFN), Propionibacterium acnes, or a combination of these drugs against experimentally induced feline infectious peritonitis (FIP). Cats were given doses of recombinant human leukocyte (alpha) IFN (rHuIFN-alpha), feline fibroblastic (beta) IFN (FIFN-beta) or P acnes at regular intervals before and after inoculation of virulent FIP virus (FIPV). Prophylactic and therapeutic administration of high doses (10(6) U/kg of body weight) or moderate doses (10(4) U/kg) of rHuIFN-alpha, FIFN-beta (10(3) u/kg), or P acnes (0.4 or 4 mg) did not significantly reduce mortality in treated vs untreated cats. However, the mean survival time in cats treated with 10(6) U of rHuIFN-alpha-/kg alone or combined with doses of P acnes was significantly (P = 0.03) increased after inoculation of highly lethal amounts (200 LD100) of FIPV vs survival time in untreated cats. Although P acnes alone was ineffective, there was some indication that a combination of P acnes and high doses of rHuIFN-alpha was more effective than rHuIFN-alpha alone. Seemingly, the efficacy of rHuIFn-alpha treatment was improved in cats challenge-exposed with less FIPV; in 1 trial, 4 of 5 cats (80%) treated with high doses of rHuIFN-alpha survived after inoculation of minimal lethal amounts (0.6 LD100) of FIPV, whereas only 2 of 5 untreated cats (40%) survived. Pretreatment of cats with 10(6) U of rHuIFN-alpha/kg resulted in detectable serum IFN activity 24 hours later; serum IFN activity was not detected in cats pretreated with P acnes, FIFN-beta, or 10(4) U of rHuIFn-alpha/kg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Virus shedding and immune responses in cats inoculated with cell culture-adapted feline infectious peritonitis virus

Eight specific pathogen-free cats were inoculated orally or parenterally with a cell culture-adapted strain of feline infectious peritonitis virus (FIPV). Faeces and oropharyngeal swabs were monitored daily for infectious virus by inoculation of feline embryo lung cells. Virus was recovered from both sites for approximately 2 weeks after inoculation, before clinical signs of disease developed. Peripheral blood lymphocytes collected from these cats were tested in an in-vitro blastogenic assay using concanavalin A (con A) and FIPV antigen. All cats showed a profound suppression of the response to con A which only recovered to pre-inoculation levels in 2 cats, one of which survived. These 2 cats also responded to FIPV antigen on the 21st day after infection, the greater response being in the survivor. The other cats, surviving 16-18 days, developed no response to FIPV antigen. Antibody titres, measured by immunofluorescence and by virus neutralization, rose rapidly to very high levels in all cats, regardless of the route of inoculation.     

Pericardial effusion in a cat with feline infectious peritonitis

This case report describes the disease progression of a male cat with pericardial effusion. Clinical signs (dyspnea, lethargy, and weakness) started very acutely. The initial laboratory profile showed only an increase in alanine aminotransferase enzyme activity. Diagnostic imaging revealed pericardial effusion. Effusion analysis showed a Rivalta-positive, modified transudate. Detection of feline coronavirus antigen in macrophages was negative. General condition and laboratory parameters dramatically worsened within seven days. Therefore, the owners decided to euthanize the cat. Even if effusion variables are macroscopically and microscopically suspicious for FIP, a definitive diagnosis of FIP could only be made by histology (including immunhistochemical staining).     

Humoral immune responses of cats to feline infectious peritonitis virus infection.

Immunoperoxidase antibody (IPA) method as a titrating method of feline infectious peritonitis (FIP) virus (FIPV) was developed for titrating antibody to FIPV (IPA-titer). By this method the immune responses of the cats that had been infected with FIPV, were traced. The infected cats could be grouped into three types by their immune response to FIPV and clinical appearances. Type I cats lived for a long time, formed a major group among infected cats, had 160 to 1 x 10(4) IPA-titers, and showed healthy appearances without any changes both on autopsy and histopathologically. From among type I cats, type II cats appeared sporadically with rapid elevation of IPA titers to 3.2 x 10(5) and showing clinical signs of FIP, and died. Type III cats lived healthily for a long time with gradual elevation of IPA-titers to a plateau of about 1 x 10(5), then showed neuronal disorder of hind leg paralysis with the descending IPA-titers to 2 x 10(4), and died. Thus, typical FIP appeared as a hyper-immune disease. Other related problems are discussed.     

Evaluation of antithrombin-III activity as a coindicator of disseminated intravascular coagulation in cats with induced feline infectious peritonitis virus infection

Six adult specific-pathogen-free cats were inoculated intraperitoneally with a cell culture-adapted strain of feline infectious peritonitis virus. Plasma samples were evaluated for antithrombin-III (AT-III) activities at post-inoculation days (PID) 0, 4, and 11 and at termination on PID 16 (1 cat) or 21 (5 cats). Other hemostatic values evaluated were activated partial thromboplastin times, prothrombin times, thrombin times, fibrinogen, platelet counts, and fibrin/fibrinogen degradation products. Antithrombin-III activity remained within normal or above normal range (89 to 246%) in all cats, with the exception of one cat on PID 4 (AT-III, 70%). Mean baseline AT-III activity for 6 cats at PID 0 was 123%. Mean AT-III activity on PID 4, 11, and 16 or 21 was 98, 162, and 130%, respectively. On PID 4 and 16 or 21, results of coagulation screening tests indicated that all cats had disseminated intravascular coagulation. Histologically, cats also had severe fibrinonecrotizing thrombovasculitis.     

Chylous abdominal effusion in a cat with feline infectious peritonitis

A 10-year-old cat was diagnosed with chyloperitoneum based on the effusion characteristics. Feline coronavirus serology was positive. The owner declined further evaluation and elected euthanasia. Necropsy revealed vasculitis with multifocal areas of necrosis and lymphocytic-plasmacytic inflammation in multiple solid organs, most likely due to feline infectious peritonitis (FIP). Immunohistochemistry was negative for FIP antigen. Notwithstanding, the final diagnosis of FIP was based on the characteristic histopathological lesions. Underlying causes of chyloperitoneum in cats and humans are discussed, and possible pathogenesis of the chyloperitoneum in association with a vasculitis such as FIP is discussed.     

Priapism in a castrated cat associated with feline infectious peritonitis

This report describes a case of feline infectious peritonitis (FIP) in a castrated cat which first presented with the unusual sign of priapism. Laboratory examinations showed increased serum protein content and decreased albumin/globulin ratio. Serum electrophoresis revealed increased alpha 2- and gamma-globulin content. One month after the first examination, the cat died. At necropsy, histopathological evaluation of organs showed inflammatory granulomatous lesions compatible with non-effusive FIP and coronavirus-specific polymerase chain reaction confirmed the diagnosis. FIP antigen was demonstrated immunohistochemically in penile tissue.     

Increased plasma levels of leukotriene B4 and prostaglandin E2 in cats experimentally inoculated with feline infectious peritonitis virus

Specific-pathogen-free kittens experimentally infected with feline infectious peritonitis virus (FIPV) subsequently demonstrated increased plasma levels of the arachidonic acid metabolites, leukotriene (LT) B4 and prostaglandin (PG) E2. Significant increases (P<0.025) in LTB4 plasma levels occurred in all (5/5) FIPV-inoculated kittens on postchallenge-exposure days (PCD) 7 and 14 vs PCD 0. Significant increases (P<0.05) in PGE2 plasma levels occurred in 80% (4/5) of FIPV-infected kittens on PCD 7 and 14. Maximal mean plasma levels of LTB4 and PGE2 occurred on PCD 7 (502.5±45.6 pg/ml and 1108.0±247.9 pg/ml, respectively). A positive correlation was found between LTB4 plasma levels and body temperature (r=0.609, P<0.01). Mean survival time in FIPV-inoculated kittens was 19.4±3.2 days. Gross lesions, including peritoneal or pleural effusions (or both) and connective tissue edema, indicated an increased vascular permeability in the FIPV-infected kittens. Histologically, lesions were characterized by pyogranulomatous inflammation. Immunofluorescent studies of tissues from FIPV-infected kittens demonstrated foci of polymorphonuclear leukocytes and FIPV-positive macrophages oriented around dilated blood vessels. Seemingly, arachidonic acid metabolites, including LTB4 or PGE2 released from macrophages, neutrophils or other cells, may be involved in the pathogenesis of FIP vascular and inflammatory lesions and in some of the clinical disease manifestations.     

Detection of feline coronavirus antibody, feline immunodeficiency virus antibody, and feline leukemia virus antigen in ascites from cats with effusive feline infectious peritonitis

To investigate the usefulness of ascites as a material for viral tests in cats with effusive feline infectious peritonitis (FIP), we attempted to detect anti-feline coronavirus antibody, anti-feline immunodeficiency virus antibody, and feline leukemia virus antigen in ascites from 88 cats clinically suspected with effusive FIP. In each of these three viral tests, all cats positive for serum antibody/antigen were also positive for ascitic antibody/antigen, while cats negative for serum antibody/antigen were also negative for ascitic antibody/antigen. This finding indicates that ascites is useful for these viral tests.     

Chemotactic responses of neutrophils in cats with spontaneous feline infectious peritonitis

The culture supernatant of peritoneal exudate cells (PEC) from cats with effusive feline infectious peritonitis (FIP) was chemotactic for peripheral blood neutrophils (PBN) from healthy cats, magnitude of the chemotactic activity being approximately 10-fold lower than that in zymosan-activated fresh serum of healthy cats (ZAS). The migration profile of PBN from healthy cats was slightly different between the PEC culture supernatant and ZAS. These findings suggest that the chemotactic activity detected in the PEC culture supernatant is distinct from that in ZAS. The chemotactic responses of PBN from FIP cats to ZAS were reduced, as compared with that from healthy controls. In contrast, the neutrophil chemotactic response and sensitivity to the PEC culture supernatant in FIP cats were not remarkably different from those in healthy controls. Furthermore, the chemotactic responsiveness of PEC from FIP cats to ZAS was slightly different from that of PEC to the PEC culture supernatant. These results suggest that neutrophils from FIP cats have altered reactivities against these chemoattractants.     

Papular cutaneous lesions in a cat associated with feline infectious peritonitis

A 7-month-old-intact male domestic shorthair cat was presented with fever, anterior uveitis in the right eye and respiratory distress when handled. These signs along with mild changes in serum protein levels and the exclusion of other potential causes were suggestive of feline infectious peritonitis (FIP). As the disease progressed, more clinical signs consistent with FIP, including renal involvement and later pleural effusion, became evident. Non-pruritic cutaneous lesions, characterized by slightly raised intradermal papules over the dorsal neck and over both lateral thoracic walls, were recognized at the end stage of the disease. The identification of papules in well-haired skin was difficult, and clipping of the fur facilitated their detection. Definitive diagnosis of FIP was made by histopathology and by immunohistochemical demonstration of coronavirus antigen in macrophages within kidney and skin lesions. The case was classified as a mixed form of FIP. Recognition of associated cutaneous lesions may facilitate a diagnosis of FIP in suspicious cases.