Nonsteroidal anti-inflammatory drugs correct the bactericidal defect of polymorphonuclear leukocytes in a guinea pig model of thermal injury.
We conducted studies to determine the effects of parenteral therapy with indomethacin, ibuprofen, and piroxicam on key immunologic and hematologic alterations induced by thermal injury. Drugs (10-20 mg/kg) or placebo were administered intramuscularly to thermally injured guinea pigs at 3 h postburn and then daily for nine days postburn. All three drugs inhibited production of 6-keto prostaglandin F1 alpha and thromboxane B2 in wound fluid and concomitantly restored the bactericidal activity of polymorphonuclear leukocytes (PMNLs) against Pseudomonas aeruginosa to normal. Indomethacin also increased the proliferative response of splenic lymphocytes to concanavalin A; however, ibuprofen and piroxicam had no effect on this response. None of the drugs affected the extent of systemic complement consumption, thrombocytopenia, leukocytosis, or leukopenia in the injured animals. These results suggest that the PMNL bactericidal defect induced by thermal injury is preventable or reversible and that the mechanisms responsible for this defect are inhibitable by nonsteroidal anti-inflammatory drugs.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D001770:Blood Bactericidal Activity / Q000187:drug effects*; D001772:Blood Cell Count; D002056:Burns / Q000188:drug therapy / Q000276:immunology*; D003165:Complement System Proteins / Q000378:metabolism; D003208:Concanavalin A / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D004195:Disease Models, Animal; D006168:Guinea Pigs; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis; D010894:Piroxicam / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013929:Thromboxane B2 / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D003208:Concanavalin A; D010894:Piroxicam; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003165:Complement System Proteins; D007052:Ibuprofen; D007213:Indomethacin