6-ketoprostaglandin-f1-alpha and Respiratory-Tract-Diseases

Protein and eicosanoid concentrations and procoagulant activity were determined in bronchoalveolar lavage fluid (BALF) from 32 Standardbred racehorses with inflammatory airway disease (IAD) and 6 control horses. Total protein, albumin and immunoglobulin G (IgG) concentrations were high (P < 0.05) in the BALF from horses with IAD, a finding consistent with exudation of plasma protein into the airway. Immunoglobulin A (IgA) concentrations also were increased (P < 0.05) which may signify local immunoglobulin production. Difference was not detected in prostaglandin E2 and 6-ketoprostaglandin F1 alpha concentrations in BALF of IAD-affected and control horses. Procoagulant activity was identified in the majority (66%) of BALF samples from IAD-affected horses and was not detected in control horses. Natural human interferon-alpha (nHulFN alpha) (placebo, 50, 150, or 450 units) was administered orally for 5 days to IAD-affected horses in a double-blind, randomised block design. Total protein, IgG, and IgA concentrations in BALF were reduced (P < 0.05) 8 days after administration of 50 u and 150 u nHuIFN alpha, and 15 days after administration of 50 u nHuIFN alpha. Procoagulant activity and albumin concentrations in BALF were lower 8 days after administration of 50 u nHuIFN alpha. Oral administration of low-dose nHuIFN alpha appeared to ameliorate these parameters of lower respiratory tract inflammation in Standardbred racehorses with IAD.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Albumins; Animals; Antiviral Agents; Bronchoalveolar Lavage Fluid; Dinoprostone; Dose-Response Relationship, Drug; Double-Blind Method; Eicosanoids; Female; Horse Diseases; Horses; Humans; Immunoglobulin A; Immunoglobulin G; Interferon-alpha; Male; Proteins; Respiratory Tract Diseases; Sports; Time Factors

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