Ibuprofen intervention in canine septic shock: reduction of pathophysiology without decreased cytokines.
This study was undertaken to evaluate the effect of a cyclooxygenase inhibitor, ibuprofen, at various time intervals in a live Escherichia coli model of canine septic shock. Group I (control) animals (n = 5) received a LD100 dose of 10(9) live E. coli per kilogram were given no further treatment. Group II animals (n = 5) received a 10 mg/kg bolus of ibuprofen 10 min prior to bacterial infusion. Group III animals (n = 5) received ibuprofen 15 min after the bacterial infusion. Statistical analysis revealed the following: Group II animals had significantly higher MABP and significantly lower levels of serum fluorescent products (superoxide radical activity), plasma thromboxane B2, prostaglandin E2, and endotoxin levels compared to Group I animals (P less than 0.05). Plasma levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6) were significantly elevated (P less than 0.05) from baseline in all animals (Groups I, II, and III), but ibuprofen treatment failed to either increase or decrease these levels. This study demonstrates that ibuprofen treatment can significantly reverse the deleterious hemodynamic and metabolic effects commonly seen in live E. coli septic shock without depressing the endogenous production of TNF or IL-6. These data support the hypothesis that sepsis initiates a cascade of mediators with the cytokines TNF and IL-6 being proximal events which in turn stimulate the next level, with ibuprofen probably exerting its inhibitory effect distal to this point in the cascade.
Coran
A G
AG
Section of Pediatric Surgery, C.S. Mott Children's Hospital, Ann Arbor, Michigan.
Drongowski
R A
RA
Paik
J J
JJ
Remick
D G
DG
D000818:Animals; D001794:Blood Pressure; D002302:Cardiac Output; D016207:Cytokines / Q000378:metabolism*; D015232:Dinoprostone / Q000097:blood; D004285:Dogs; D004731:Endotoxins / Q000097:blood; D004927:Escherichia coli Infections; D007052:Ibuprofen / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000378:metabolism; D015227:Lipid Peroxidation; D012772:Shock, Septic / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D013481:Superoxides / Q000097:blood; D013929:Thromboxane B2 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D004731:Endotoxins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D013929:Thromboxane B2; D015232:Dinoprostone; D007052:Ibuprofen