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

Abstract

Summary 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 (α) ifn (rHuIFN-α), feline fibroblastic (β) ifn (FIFN-β) or P acnes at regular intervals before and after inoculation of virulent fip virus (fipv). Prophylactic and therapeutic administration of high doses (106 U/kg of body weight) or moderate doses (104 U/kg) of rHuIFN-α, FIFN-β (103 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 106 U of rHuIFN-α-/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-α was more effective than rHuIFN-α alone. Seemingly, the efficacy of rHuIFN-α treatment was improved in cats challenge-exposed with less fipv; in 1 trial, 4 of 5 cats (80%) treated with high doses of rHuIFN-α 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 106 U of rHuIFN-α/kg resulted in detectable serum ifn activity 24 hours later; serum ifn activity was not detected in cats pretreated with P acnes, fifn-β, or 104 U of rHulFn-α/kg. After inoculation of fipv, increase in serum ifn activity and virus-neutralizing antibody (vna) titer was observed in treated or untreated cats, but increase in serum ifn activity or vna titer was not associated with protective immunity. In contrast to untreated cats, those treated with high doses of rHuIFN-α had temporary suppression of clinical signs of fip and decreased serum ifn or vna responses to fipv, suggesting some antiviral or immunomodulatory (or both) activities. Immunomodulation by rHuIFN-α in cats inoculated with fipv also was suggested by necropsy findings of increased paracortical hyperplasia and decreased necrosis in lymphoid tissues of ifn-treated vs untreated cats. Results indicated that intensive treatment alone with ifn or P acnes failed to protect most cats against fatal disease after challenge exposure with lethal doses of fipv. High doses of rHuIFN-α alone or combined with P acnes, however, temporarily suppressed disease signs and extended survival time, suggesting a potential role of rHulFN-α as adjunctive, rather than primary, treatment for fip.