Ibuprofen attenuates early lung injury in endotoxemic, neutropenic rats.
The objective of our study was to determine the role of ibuprofen in protecting neutropenic rats from cardiopulmonary injury due to endotoxemia. We hypothesized that ibuprofen would offer pulmonary protection by altering cytokine production. Neutropenic rats received E. coli lipopolysaccharide (LPS) alone or ibuprofen and LPS. After 4 h, arterial blood gases, heart rate and blood pressure were measured. Blood and bronchoalveolar lavage fluid (BALF) were collected for TNF- alpha and MIP-2 concentrations. Lung tissue for iNOS mRNA and myeloperoxidase were obtained. The ibuprofen group had decreased heart rate and better oxygenation. Ibuprofen suppressed TNF- alpha and MIP-2 production in blood and MIP-2 concentrations in BALF. Lung mRNA for iNOS was higher in the ibuprofen group. Neutrophil infiltration in the lung was similar in both groups. Ibuprofen attenuated cardiopulmonary dysfunction by decreasing the early cytokine response. The balance of vasodilator to vasoconstrictor production in the lung may favor vasodilation as shown by increased iNOS mRNA and suppression of thromboxane.
Daphtary
K M
KM
Critical Care Medicine, Children's Hospital of Michigan, Wayne State University, Detroit, MI 48201, USA.
Heidemann
S M
SM
Glibetic
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid; D054426:Chemokine CXCL2; D018925:Chemokines / Q000096:biosynthesis; D003520:Cyclophosphamide / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D019446:Endotoxemia / Q000188:drug therapy*; D006439:Hemodynamics; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D007249:Inflammation; D008168:Lung / Q000378:metabolism; D008297:Male; D009503:Neutropenia / Q000188:drug therapy*; D009504:Neutrophils / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D016207:Cytokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003520:Cyclophosphamide; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D007052:Ibuprofen