Abstract

In humans, type 1 interferons (IFN-α and IFN-β) play an important role in host defense against viral infections, and in the establishment of the innate immune response prior to the production of specific anti-viral antibodies. Recombinant IFN-α is used widely in clinical treatments as an antiviral or antineoplastic agent, and recombinant IFN-β is also used for treatment of relapsing-remitting multiple sclerosis. In these remedies, IFN-α and IFN-β are mostly administered parenterally at high doses. Toxicity is frequently the limiting factor, however, in the clinical application of interferons. On the other hand, there are a number of clinical reports on the oral administration of low doses of IFNs to patients suffering from autoimmune diseases. In vivo experiments of oral low-dose IFN-α treatment have been described in many animal species (e.g., cattle, pigs, and horses). Such treatment was shown to lead to dramatic clinical amelioration in animal models of both infectious and chronic inflammatory diseases. In marine mammals, the efficacy of IFNs is not well documented.

In 2008, a 10-year-old bottlenose dolphin (Tursiops truncatus) with no clinical signs showed moderate leukopenia (2200/µl) with definitive neutropenia (1100/µl). All other hematological and serum analyses appeared to be normal. The dolphin was slightly underweight. Vibrio sp. was isolated from her fecal sample. Fungus was detected in the blowhole culture, although the dolphin did not show any clinical signs of respiratory disorder. Blood culture showed no bacterial growth.

Oral low-dose human IFN-α therapy was initiated, by administration of 200 IU IFN-α once daily PO for 12 weeks. The oral route of administration had obvious advantages for ease of handling and owner's compliance. This treatment resulted in a gradual improvement of the leukopenia, accompanied by a slow increase of neutrophil count. Interestingly, the improvement of the neutrophil count occurred at approximately the same time as the recovery from Vibrio sp. in her fecal. It was suggested that with this treatment, we could prevent opportunistic infection, possibly by eliciting the innate immune response.

Our case study supports the hypothesis that oral low-dose IFN-α treatment induced the intrinsic innate immune response in bottlenose dolphin. If this is the case, such IFN-α treatment might be useful for other immunocompromised conditions or viral diseases in bottlenose dolphin. Further studies are needed to better understand the efficacy of interferon treatment in immunocompromised or virally infected bottlenose dolphins.