|Kehrli Jr, Marcus|
Submitted to: Porcine Reproductive and Respiratory Syndrome International Symposium
Publication Type: Abstract Only
Publication Acceptance Date: 10/3/2011
Publication Date: 12/2/2011
Citation: Schlink, S.N., Lager, K.M., Brockmeier, S.L., Loving, C.L., Henningson, J.N., Faaberg, K.S., Guo, B., Miller, L.C., Vorwald, A.C., Kehrli, Jr., M.E. 2011. Enhancement of innate immunity with granulocyte colony-stimulating factor did not prevent disease in pigs infected with a highly pathogenic Chinese PRRSV strain. 2011 International PRRS Symposium. Paper No. 59. page 76. Interpretive Summary:
Technical Abstract: Chinese highly pathogenic PRRSV (HP-PRRSV) strain JXwn06 has been shown to produce high fevers, loss of body condition, respiratory distress and death in pigs. Necropsy reveals extensive interstitial pneumonia, multi-systemic pathology and a high occurrence of secondary bacterial infections. The fulminant bacterial disease suggests dysregulation of the immune system that allows subclinical bacterial infections to become a major cause of morbidity and mortality in HP-PRRSV infected swine. We hypothesized that by enhancing innate immunity through administration of granulocyte colony-stimulating factor (G-CSF) we might attenuate secondary bacterial disease and the clinical effects of HP-PRRSV infection. G-CSF is a cytokine that stimulates production and release of functional granulocytes from the bone marrow and is used in humans to reduce the chance of infection in selected cancer patients receiving chemotherapy medications that induce neutropenia. Four-week-old pigs obtained from a PRRSV free herd were randomly assigned to treatment groups in a 2 X 2 design. Pigs received either an intramuscular injection of 10**10 TCID50/ml adenovirus vectored G-CSF (Ad5-GCSF, n=30) or adenovirus vector with no insert (Ad5-empty, n=30) on day -3, and on day 0 received an intranasal challenge with 2 ml HP-PRRSV 10**4 TCID50/ml. A combination of Ad5-GCSF treated (n=5) and Ad5-empty treated (n=10) pigs served as sham inoculated controls. At the time of HP-PRRSV challenge, pigs treated with Ad5-GCSF exhibited a significant neutrophilia in response to the vectored G-CSF (>6 times increase in neutrophils by day 0). Despite G-CSF treatment, all pigs challenged with HP-PRRSV began exhibiting signs of disease by day 2 and had a rapid paradoxical decline in neutrophils to baseline levels. Disease progressed to 100% morbidity and mortality in both HP-PRRSV challenged groups. In contrast, non-virus challenged, Ad5-GCSF treated control pigs remained healthy and had a neutrophilia for the duration of the study. This study confirms the highly virulent nature of HP-PRRSV and its ability to easily overcome host defenses leading to disease and secondary bacterial infection.