Targeting Neutrophil-CXCR2 For The Treatment Of Influenza Pneumonia | 68512
Primary Healthcare: Open Access
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Complications of acute respiratory distress syndrome (ARDS), a severe form of acute lung injury, remain major cause of
death in influenza pneumonia. Several recent studies have demonstrated that considerable lung damage is contributed
by the host immune response in addition to the cytopathic effects of the influenza virus. Previously, we have demonstrated
that excessive neutrophils recruitment and their generated neutrophil extracellular traps (NETs) contribute to pathologic
complications of ARDS in severe influenza pneumonia in mice. Neutrophils express predominantly CXC chemokine receptors
including CXCR1 and CXCR2, which play key role in the recruitment and activation of neutrophils. This study was aimed to
test the therapeutic potential of CXCR1/2 antagonism in severe influenza pneumonia. Our results have shown high increase in
CXCR2 expression in both circulating and lung-recruited neutrophils. We used a selective CXCR1/2 antagonist, SCH527123
alone or in combination of an anti-vial agent, oseltamivir. BALB/c female mice were challenged with lethal influenza A/
PR/8/34 (H1N1), 2500 pfu. Oseltamivir or SCH527123 were administered orally. Treatment with oseltamivir alone showed
15% survival, while all animals were died in SCH527123 alone treatment group. However the combined administration of
these drugs resulted in 60% to 100% survival in mice after lethal influenza infection. The addition of SCH527123 to the
combination therapy regime was also found to significantly alleviate lung pathology, compared to oseltamivir treatment
alone. Lungs of infected animals following combination therapy showed decreased neutrophil influx, decreased release of
extracellular histones, reduced vascular leakage, and reduced alveolar capillary damage. These results demonstrate that the use
of CXCR1/2 antagonists in combination with a classical antiviral therapy can be a novel and effective treatment approach for
severe influenza pneumonia.
Narasaraju Teluguakula has received his PhD from Osmania University, India and Post-doctoral training from Center for Veterinary Health Sciences, Oklahoma State University and at School of Medicine, National University of Singapore. He has published more than 30 papers in reputed journals mainly related to respiratory biology and pathology. Currently, he is working as a Project Leader at Oklahoma Center for Respiratory and Infectious Diseases and Assistant Professor at Oklahoma State University, USA.