Role of Leukotrienes in Rat Reversed Passive Arthus Pleurisy and the Effect of AA-861, a 5-Lipoxygenase Inhibitor

Abstract

In studies of the role of leukotrienes in inflammatory reactions, the induction of rat reversed passive Arthus pleurisy (a type III allergic reaction) was employed. Increases of exudate volume, vascular permeability, and migration of inflammatory cells in the pleural cavity were observed. The vascular permeability was enhanced biphasically during 0–30 min (early response) and during 3–6 h (late response) after induction of the pleurisy. The infiltration of inflammatory cells, mainly polymorphonuclear leukocytes, into the cavity increased and reached a maximum 6 h after the pleurisy was induced. Leukotriene B₄ (LTB₄), 5-monohydroxyeicosatetraenoic acid (5-HETE), and slow-reacting substance of anaphylaxis (SRS-A), consisting of LTC₄, LTD₄ and LTE₄, were detected in the exudate by reversed-phase high-performance liquid chromatography during the early response. The contents of LTC₄ reached a maximum 10 min after the challenge, followed by a rapid decrease within 1 h. The rise and decay of LTC₄ correlated with the increase in vascular permeability during the early phase. AA-861, a 5-lipoxygenase inhibitor, given intrapleurally inhibited the increase in vascular permeability, cell migration, and generation of leukotrienes during the early phase of the pleurisy. These results indicate that products of the 5-lipoxygenase pathway, such as LTC₄ and LTB₄, may play an important role as chemical mediators in the inflammatory reaction.

Effects of Quinotolast, a New Orally Active Antiallergic Drug, on Experimental Allergic Models

“…The mechanism for this inhibition is not clear, but the inhibition of release of chemical mediators such as histamine and pLTs from inflammatory cells may be relevant (29).…”

Augmentation of reverse arthus reaction by mast cells in mice.

“…In the present study, 100 mg/kg of A-63162 inhibited leukocyte influx only by 40% and edema by 60%. Makino et al (19) and Tanaka et al (18) also observed only a partial inhibition of leukocyte influx and plasma exudation in immune complexinduced pleurisy in the rat after treatment with a 5-lipoxygenase antagonist. Therefore, mediators other than leukotrienes are also involved in these processes.…”

Anti-inflammatory Compounds from the Leaves of Ailanthus altissima Meihua JIN

“…As the results, 2, 4, and 5 strongly inhibited both the COX-2-dependent PGD 2 generation with IC50 values of 2.6, 7.3 and 2.5 μM, respectively and the generation of LTC4 in the 5-LOX dependent phase with IC 50 values of 2.0, 5.1 and 1.8 μM, respectively (Table II). In this experiments, NS398 (COX-2 selective inhibitor) and AA861 (5-LOX inhibitor) were used as positive control (Makino et al, 1986;Ouellet et al, 1995). Under the same conditions, NS398 and AA861 strongly inhibited PGD2 and LTC4 generation of bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with an IC 50 of 1.6×10 −4 μM and 3.2×10 −2 μM, respectively.…”