Pretreatment with Ibuprofen Augments Circulating Tumor Necrosis Factor-α, Interleukin-6, and Elastase during Acute Endotoxinemia

Plasma levels of tumor necrosis factor-α (TNFα), 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 TNFα concentrations with maximal levelsat 90 min (369 ± 44 pg/ml, P < .001 vs. saline controls, n = 7). The rise in TNF-α 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 TNFα 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 TNFα was paralleled by increased levels of circulating elastase. In vitro experiments suggest a causal relationship between these events. Thus, the cyclooxygenaseinhibitor ibuprofen blunts the clinical response to endotoxin but augments circulating cytokine levels and leukocyte degranulation.