thromboxane-b2 and Respiratory-Tract-Diseases

Topics: Animals; Dogs; Guinea Pigs; Humans; Inflammation; Rabbits; Respiratory Hypersensitivity; Respiratory Tract Diseases; Thromboxane B2

Cineole (eucalyptol) is the isolated active agent of eucalyptus oil. Traditionally, it is recommended for treating the symptoms of airway diseases exacerbated by infection. We have examined the inhibitory effect of 1.8-cineole on LPS-and IL1beta-stimulated mediator production by human monocytes in vitro. For the first time, we report on a dose-dependent and highly significant inhibition of production of tumor necrosis factor-alpha, interleukin-1beta, leukotriene B4 and thromboxane B2 by 1.8-cineole. In summary, this is the first report on a new mechanism of action of monoterpenes suggesting 1.8-cineole as a strong inhibitor of cytokines that might be suitable for longterm treatment of airway inflammation in bronchial asthma and other steroid-sensitive disorders.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Asthma; Cyclohexanols; Cytokines; Eucalyptol; Female; Humans; In Vitro Techniques; Inflammation; Inflammation Mediators; Interleukin-1; Leukotriene B4; Lipopolysaccharides; Male; Menthol; Monocytes; Monoterpenes; Respiratory Tract Diseases; Terpenes; Thromboxane B2; Tumor Necrosis Factor-alpha

NS-398 (N-(2-cyclohexyloxy-4-nitrophenyl) methane sulphonamide), a newly synthesized potent non-steroidal anti-inflammatory drug (NSAID) has a much lesser degree of toxicity, as compared with presently available NSAIDs. We have investigated the inhibition of prostanoid production in inflammatory exudate, gastric mucosa and renal papillary tissue, following oral administration to carrageenan-air-pouch rats. The ID50 values of NS-398 in the inflammatory exudate, gastric mucosa and renal papillary tissue were 0.18, 62.2 and 261.7 mg kg-1, respectively. In contrast, indomethacin decreased the PGE2 concentration in the inflammatory exudate, gastric mucosa and renal papillary tissue, with the same dose range, the ID50 values being 0.23, 0.14 and 0.15 mg kg-1, respectively. The same tendency was seen for 6-keto-prostaglandin F1 and thromboxane B2. Moreover, NS-398 inhibited excess PGE2 production in inflamed tissue but did not affect physiological production of PGE2 in non-inflamed tissue. Indomethacin, in both inflamed and non-inflamed tissues, inhibited PGE2 production to the same degree. These results indicated that NS-398 has some specificity for inflamed tissue, by inhibiting prostanoid synthesis, and this effect may explain the decreased side-effects of this drug.

Topics: 6-Ketoprostaglandin F1 alpha; Air Sacs; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Dinoprostone; Exudates and Transudates; Gastric Mucosa; Indomethacin; Inflammation; Kidney; Nitrobenzenes; Prostaglandins; Rats; Respiratory Tract Diseases; Sulfonamides; Thromboxane B2