leukotriene-b4 and acetylsalicylic-acid-lysinate

Topics: Adult; Arachidonic Acids; Aspirin; Creatinine; Cyclooxygenase Inhibitors; Enzyme-Linked Immunosorbent Assay; Female; Histocompatibility Testing; Humans; Kidney Transplantation; Leukotriene B4; Lysine; Male; Middle Aged; Prostaglandins F; Thromboxane B2

Aspirin-exacerbated respiratory disease (AERD) is characterized by severe, sometimes life-threatening reactions to nonsteroidal anti-inflammatory drugs (NSAIDs). Mechanisms driving the disease include overproduction of leukotrienes and loss of anti-inflammatory prostaglandin E. To investigate the capacity of aspirin and NSAIDs to drive eosinophil activation and the ability of PGE. Eosinophils were purified from blood of healthy individuals without AERD and stimulated with lysine aspirin, ketorolac, or sodium salicylate. The role of PGE. Stimulation of eosinophils with lysine aspirin, ketorolac, or sodium salicylate resulted in secretion of CysLTs and LTB. Eosinophils can be directly activated by NSAIDs via cyclooxygenase-independent pathways to produce CysLTs and LTB

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cells, Cultured; Cysteine; Dinoprostone; Drug Hypersensitivity; Eosinophils; Humans; Ketorolac; Leukotriene B4; Leukotrienes; Lysine; Sodium Salicylate

To test the hypothesis that alveolar macrophages (AM) from wheezy infants release increased amounts of eicosanoids, as do AM from adults with asthma, we compared eicosanoid release by unstimulated- and ionophore-A23187-stimulated AM from 13 wheezy and six nonwheezy infants and analyzed its regulation by dexamethasone in vitro. Alveolar macrophages from wheezy infants released greater amounts of thromboxane A2 (TxA2) and leukotriene B4 (LTB4) under resting conditions and of TxA2 upon stimulation than did those from control subjects. Dexamethasone induced a dose-dependent inhibition of the spontaneous and A23187-stimulated release of TxA2, but not of the A23187-stimulated release of lipoxygenase products. The inhibition of TxA2 formation was maintained when free arachidonic acid was added during A23187 stimulation, demonstrating that dexamethasone acted mainly at a postphospholipase A2 site. AM exposed to acetylsalicylate and then incubated overnight exhibited de novo cyclooxygenase synthesis, suggesting the presence of the inducible cyclooxygenase as a target for inhibition by dexamethasone. In conclusion, our findings suggest that AM from wheezy infants are activated in vivo to release eicosanoids, as are AM from asthmatic adults, and they support the therapeutic indications of glucocorticoids in severe recurrent wheezing of infancy.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Aspirin; Calcimycin; Case-Control Studies; Dexamethasone; Dose-Response Relationship, Drug; Female; Glucocorticoids; Humans; In Vitro Techniques; Infant; Ionophores; Leukotriene B4; Lysine; Macrophages, Alveolar; Male; Respiratory Sounds; Thromboxane A2