Role of IFN-alpha during the acute stage of a swine influenza virus infection.

Cytokines, especially interferon-alpha (IFN-alpha) are important in controlling influenza virus infections. To investigate the role of IFN-alpha in influenza, the swine IFN-alpha neutralizing monoclonal antibody (Ab) K9 was applied in a swine model of influenza A virus infection. First, the optimal dose and route for administration of the IFN-alpha neutralizing Abs was determined. Based on those results, the effect of the Abs on a swine influenza virus infection was investigated. Pigs were inoculated intratracheally with 10(6.0) mean egg infectious dose (EID(50)) A/Swine/Belgium/1/98 (H1N1) virus. At the time of challenge and 18 h later, they were injected intratracheally and intraperitoneally with a high dose of IFN-alpha neutralizing Abs or control Abs. The animals were euthanized at 0, 24, 30, 48 and 72 h after inoculation. At 24 and 30 h, IFN-alpha levels in broncho-alveolar lavage fluid of K9 recipient animals were strongly suppressed, and this coincided with reduced IL-6 and IL-12 levels. TNF-alpha and IL-1 levels were unaffected compared to those in the control Ab treated group. Importantly, the onset and peak of clinical symptoms in IFN-alpha neutralizing Abs treated animals were delayed by 24h, simultaneously with the suppression of IFN-alpha, but there was no obvious effect on virus replication and lung pathology. These results suggest an important role for IFN-alpha in IL-6 and IL-12 induction and a role of all three cytokines in the symptoms of swine influenza.