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.
Barbé
Filip
F
Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Saelens
Xavier
X
Braeckmans
Debby
D
Lefèvre
François
F
Reeth
Kristien Van
KV
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype; D016898:Interferon-alpha / Q000502:physiology*; D018664:Interleukin-12 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D008168:Lung / Q000276:immunology / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000662:veterinary*; D013552:Swine / Q000821:virology; D013553:Swine Diseases / Q000276:immunology / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D019562:Viral Load / Q000662:veterinary
D000911:Antibodies, Monoclonal; D016898:Interferon-alpha; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12