ost-treatment with the PPAR-gamma agonist pioglitazone inhibits inflammation and bacterial growth during Klebsiella pneumoni

Author(s)

Ramirez-Moral, Ivan ^{[1, 2, 3]} ; Ferreira, Bianca Lima ^{[1, 2, 4]} ; de Vos, Alex F. ^{[1, 2]} ; van der Poll, Tom ^{[1, 5]}

Affiliation

^[1] Univ Amsterdam, Ctr Expt & Mol Med, Amsterdam UMC, Amsterdam - Netherlands

^[2] Amsterdam Infect & Immun Inst, Amsterdam - Netherlands

^[3] Univ Amsterdam, Locat Acad Med Ctr, Amsterdam UMC, Meibergdreef 9, Room G2-130, NL-1105 AZ Amsterdam - Netherlands

^[4] Univ Fed Sao Paulo, Escola Paulista Med, Dept Med, Div Infect Dis, Sao Paulo - Brazil

^[5] Univ Amsterdam, Div Infect Dis, Amsterdam UMC, Amsterdam - Netherlands

• Document type: Journal article
• Source: RESPIRATORY RESEARCH; v. 22, n. 1 AUG 19 2021.
• Web of Science Citations: 2

Abstract

Agonists of peroxisome proliferator-activated receptor (PPAR)-gamma have been suggested as potential adjuvant therapy in bacterial pneumonia because of their capacity to inhibit inflammation and enhance bacterial clearance. Previous studies only assessed the effects of pretreatment with these compounds, thereby bearing less relevance for the clinical scenario. Moreover, PPAR-gamma agonists have not been studied in pneumonia caused by Klebsiella pneumoniae, a common human respiratory pathogen of which antibiotic treatment is hampered by increasing antimicrobial resistance. Here we show that administration of the PPAR-gamma agonist pioglitazone 6 or 8 h after infection of mice with a highly virulent strain of Klebsiella pneumoniae via the airways results in reduced cytokine and myeloperoxidase levels in the lungs at 24 h after infection, as well as reduced bacterial growth in the lungs and decreased dissemination to distant organs at 42 h post-infection. These results suggest that pioglitazone may be an interesting agent in the treatment of Klebsiella pneumonia. (AU)

• FAPESP's process: 19/02224-0 - Metabolism in airway epithelium and immune cells during homeostasis and inflammation
• Grantee: Bianca Rodrigues Lima Ferreira
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate