A possible role of prostaglandins and bradykinin as a trigger of exudation in carrageenin-induced rat pleurisy

Abstract

Pleurisy was induced in rats after intrapleural injection of 2% ~,-carrageenin. The volume of the pleural exudate increased rapidly between 1 and 3 h, continuing to increase until 7 h. The dye amounts exuded into the pleural cavity for 20 min after 5% pontamine sky blue (60 mg/kg, i.v.) increased markedly at 1 to 3 h, then they kept constant until 6 h, decreasing thereafter. The PGE level in the pleural fluid increased rapidly during the period from 1 to 3 h, when the exudate commenced to accumulate, and then decreased slightly until 7 h. The main PG in the pleural fluid was recognized as PGE 2 on thln-layer chromatography. The pretreatment of rats with a PG synthetase inhibitor, indomethaeln (5 mg/kg, i.p.), 30 rain before earragecnin administration resulted in the significant reduction of dye leakage at 1 h and of the pleural fluid exudation at 1 to 3 h. The intravenous injection into rats of stem bromelain (10 mg/kg, i.v.), a SH-protease from pineapples, caused the depletion of high molecular weight kininogen in plasma without effect on the content of low molecular weight kininogen. The pretreatment of rats with bromelain 30 rain before carrageenln caused a marked reduction in the dye exudation during the periods from 1 to 3 h and 5 to 6 h. The accumulation of the exudate was strongly suppressed at the same periods. Although each treatment by itself did not completely abolish the dye and fluid exudation, the treatment of rats simultaneously with indomethaeln and bromelain resulted in suppression of dye leakage from 1 to 6 h and practically no fluid accumulation was observed until 4 h. These results strongly indicate that prostaglandln is released in combination with bradykinin at the period when the pleural exudate commences to accumulate.Bradykinin is believed to be one of the potent chemical mediators in inflammation, because of its characteristic pro-inflammatory pharmacological properties. The E series of prostaglandins have been added recently to the list of candidates for mediators, because of their pharmacological features.A possible involvement of prostaglandins in inflammation has been further strengthened by the fact that therapeutic doses of non-steroidal anti-inflammatory agents inhibit prostaglandin biosynthesis in vivo as well as in vitro.In spite of the above-mentioned features favorable to inflammation the ability of prostaglandins to increase vascular permeability is, in fact, negligible in guinea pigs [1], or much weaker than bradykinin in rabbits [2], when labelled albumin is used, or when the exuded dye is extracted. These unfavorable findings have been overcome by the fact that the threshold doses of prostaglandin potentiate the activity of other mediators, including bradykinin, to increase vascular permeability in guinea pigs [1], rabbits [2], and rats [3][4][5], in skin and paws. Thus, prostaglandins can be considered to act as a modulator at inflammatory sites.The present experiments were performed to examine whether prostaglandins may play the same role as a modulator in an in ...

Suppression of inflammatory responses to 12‐O‐tetradecanoylphorbol‐13‐acetate and carrageenin by YM‐26734, a selective inhibitor of extracellular group II phospholipase A2

“…The accumulation of exudate fluid and leukocytes into the pleural cavity in response to carrageenin injection appears to be regulated by metabolites of AA for the following reasons. Carrageenin injection causes accumulation of PGE2 (Katori et al, 1978), LTB4 (Flower et al, 1986) and LTC4/D4 (Ueno et al, 1983), and many inhibitors of cyclooxygenase, 5-lipoxygenase, or both suppress both plasma exudation and leukocyte migration induced by carrageenin (Ashida et al, 1983;Ku et al, 1988). YM-26734 also inhibited accumulation of exudate fluid and leukocytes into the pleural cavity, suggesting that extracellular group II PLA2 may play a role in this inflammatory process.…”

Critical Role of L-Selectin and Histamine H4 Receptor in Zymosan-Induced Neutrophil Recruitment from the Bone Marrow: Comparison with Carrageenan

“…These inflammatory cells synthesize and release various mediators of inflammation, among which the kallirein-kinin system and prostaglandins play a pivotal role. Inhibitors of cyclooxygenase, kallikreinkinin, and bradykinin are capable of blocking carrageenaninduced pleurisy in vivo (Katori et al, 1978;Dozen et al, 1989). Previous experiments have shown that neutrophil migration is reduced by agents capable of blocking the release of a specific neutrophil attractant from macrophages (Moraes et al, 1993).…”

In vivo and in vitro Effects of Bromelain on PGE₂ and SP Concentrations in the Inflammatory Exudate in Rats

“…Anecdotal use of this drug includes the treatment of inflamed joints, postsurgical inflammatory pain, visceral inflammatory diseases, and urogenital inflammation [4][5][6]. In the past, it was reported that bromelain exerts anti-inflammatory effects in some rat models such as the carrageenin-induced pleurisy [7], and the kaolin-induced inflammation of an air pouch [8]. However, the mechanisms of the anti-inflammatory action of bromelain have not been fully elucidated, beginning from its effect on the generation of classic proinflammatory mediators in the site of inflammation.…”