Pretreatment with ibuprofen augments circulating tumor necrosis factor-alpha, interleukin-6, and elastase during acute endotoxinemia.
Plasma levels of tumor necrosis factor-alpha (TNF alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6) were monitored after intravenous administration of Escherichia coli endotoxin with or without ibuprofen pretreatment to healthy volunteers. Intravenous endotoxin (n = 7) resulted in elevated plasma TNF alpha concentrations with maximal levels at 90 min (369 +/- 44 pg/ml, P less than .001 vs. saline controls, n = 7). The rise in TNF-alpha was followed by a rise in plasma IL-6 (27 +/- 12.8 ng/ml), peaking 30-90 min thereafter. Pretreatment with ibuprofen (n = 6) caused a significant augmentation and temporal shift in cytokine elaboration with maximal TNF alpha levels (627 +/- 136 pg/ml) at 120 min and IL-6 peaks (113 +/- 66 ng/ml) at 180 min. In ibuprofen-treated volunteers, the additional increase in TNF alpha was paralleled by increased levels of circulating elastase. In vitro experiments suggest a causal relationship between these events. Thus, the cyclooxygenase inhibitor ibuprofen blunts the clinical response to endotoxin but augments circulating cytokine levels and leukocyte degranulation.
Spinas
G A
GA
Department of Internal Medicine, University Hospital, Basel, Switzerland.
Bloesch
D
D
Keller
U
U
Zimmerli
W
W
Cammisuli
S
S
D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure; D001831:Body Temperature; D015550:Cell Degranulation; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli; D006339:Heart Rate; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D016018:Least-Squares Analysis; D007958:Leukocyte Count; D008297:Male; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology; D010196:Pancreatic Elastase / Q000097:blood*; D012044:Regression Analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D004731:Endotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D010196:Pancreatic Elastase; D007052:Ibuprofen