Adjunctive dexamethasone therapy improves lung injury by inhibiting inflammation and reducing RIP3 expression during Staphylococcus aureus pneumonia in mice

• Published in: International immunopharmacology 2014-12, Vol.23 (2), p.709-718
• Main Authors: Wen, Shun-hang, Wu, Hu-jun, Lin, Li, Chong, Lei, Zhu, Li-li, Zhang, Wei-xi, Zhang, Hai-lin, Li, Chang-chong
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - therapeutic use; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - therapeutic use; Cytokines - antagonists & inhibitors; Cytokines - immunology; Dexamethasone; Dexamethasone - administration & dosage; Dexamethasone - therapeutic use; Drug Therapy, Combination; Female; Inflammation; Lung - drug effects; Lung - immunology; Lung - pathology; Lung Injury - etiology; Lung Injury - immunology; Lung Injury - prevention & control; Mice, Inbred C57BL; Oxacillin - administration & dosage; Oxacillin - therapeutic use; Pneumonia; Pneumonia, Staphylococcal - complications; Pneumonia, Staphylococcal - drug therapy; Pneumonia, Staphylococcal - immunology; Receptor-Interacting Protein Serine-Threonine Kinases - antagonists & inhibitors; Receptor-Interacting Protein Serine-Threonine Kinases - genetics; RIP3; Staphylococcus aureus; Staphylococcus aureus - drug effects
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2014.10.027

Antibiotic-induced immunopathology associated with the release of bacterial cell wall components has been suggested to contribute to poor outcomes in bacterial pneumonia. Adjunctive systemic glucocorticoid steroid (GC) therapy for pneumonia has been a controversial issue. In the present study, we first found that dexamethasone (2.5mg/kg/day) in combination with oxacillin was beneficial for improving lung injury in mice inoculated intratracheally with live Staphylococcus aureus, and did not interfere with bacterial clearance. Alleviation of lung injury was evidenced by attenuated lung pathology, reduced total protein levels, soluble receptor for advanced glycation end-products (sRAGE), tumor necrosis factor alpha (TNF-α), and keratinocyte chemoattractant (KC) and interleukin (IL)-6 in bronchoalveolar lavage fluid (BALF). It was further confirmed by inhibition of receptor interacting protein-3 (RIP3) expression in pulmonary tissues. As in the live S. aureus experiments, dexamethasone (2.5mg/kg/day) improved lung injury in mice challenged with heat-killed S. aureus (HKSA). In conclusion, our results demonstrated that an appropriate dose of adjunctive dexamethasone (2.5mg/kg/day) with oxacillin alleviated experimental S. aureus-induced lung injury via its inhibition of inflammatory cytokine release and RIP3 expression. •Adjunctive dexamethasone protects against S. aureus-induced lung injury in mice.•Protection is via inhibition of inflammation and the reduction of RIP3 expression.•Dexamethasone protects against heat-killed S. aureus-induced lung injury in mice.