Cyclooxygenase-2-Derived Prostaglandin E2 and Lipoxin A4 Accelerate Resolution of Allergic Edema inAngiostrongylus costaricensis-Infected Rats: Relationship with Concurrent Eosinophilia

Abstract

In noninfected rats, challenge with allergen following local IgE sensitization induced a pleurisy marked by intense protein exudation that plateaued from 30 min to 4 h after challenge, reducing thereafter. Infection of rats with Angiostrongylus costaricensis induced a 5-fold increase in blood eosinophil numbers by 25 days postinfection, whereas the numbers of eosinophils in the pleural cavity ranged from normal to a weak increase. In infected rats, identically sensitized, challenge with Ag induced a much shorter duration of pleural edema with complete resolution by 4 h, but no change in the early edema response. In parallel, infection increased the number of eosinophils recovered from the pleural cavity at 4 h, but not at 30 min, following allergen challenge. Pretreatment with IL-5 (100 IU/kg, i.v.) also increased eosinophil numbers in blood and, after allergen challenge, shortened the duration of the pleural edema and increased pleural eosinophil numbers. There were increases in the levels of both PGE2 and lipoxin A4 (LXA4) in pleural exudate. Selective cyclooxygenase (COX)-2 inhibitors, NS-398, meloxicam, and SC-236, did not alter pleural eosinophilia, but reversed the curtailment of the edema in either infected or IL-5-pretreated rats. Pretreatment of noninfected animals with the PGE analogue, misoprostol, or two stable LXA4 analogues did not alter the magnitude of pleural exudation response, but clearly shortened its duration. These results indicate that the early resolution of allergic pleural edema observed during A. costaricensis infection coincided with a selective local eosinophilia and seemed to be mediated by COX-2-derived PGE2 and LXA4.

An Aspirin-Triggered Lipoxin A4 Stable Analog Displays a Unique Topical Anti-Inflammatory Profile

“…The pronounced efficacy of ATLa on edema formation as well as on neutrophil and eosinophil cell infiltration in this model is the first demonstration that lipoxin analogs can modulate a cutaneous, T cell-dependent allergic response. These results are consistent with earlier studies showing that lipoxin analogs inhibit eosinophil chemotaxis in vitro (39) and eosinophil-driven inflammation in vivo (13,14). Taken together these findings suggest that ATLa could be explored for topical treatment of dermatoses with a prominent eosinophil component, such as allergic contact dermatitis or atopic dermatitis.…”

“…More specifically, lipoxins inhibit cytokine-stimulated IL-1␤, macrophage inflammatory protein-2, and superoxide production while stimulating the anti-inflammatory cytokine IL-4 in neutrophils (11). Eosinophil-driven allergic reactions are also inhibited by stable LXA 4 analogs (13,14). Lipoxins inhibit eosinophil chemotaxis, and IL-5 and eotaxin secretion (13).…”

Lipopolysaccharide-Induced Increase of Prostaglandin E2 Is Mediated by Inducible Nitric Oxide Synthase Activation of the Constitutive Cyclooxygenase and Induction of Membrane-Associated Prostaglandin E Synthase

“…Moreover, an i.p. injection of 0.5 mg/kg SC-236 was sufficient to entirely reverse the curtailment of the edema evoked by allergen in infected rats (28). No toxicity was elicited by administration of up to 200 mg/kg SC-236 in rats (27).…”

Cyclooxygenase 2 Plays a Pivotal Role in the Resolution of Acute Lung Injury

“…A late, antiinflammatory effect of COX-2, instead of the more widely appreciated early, proinflammatory action, was crucial to the timely recovery from ALI. Similarly, COX-2-catalyzed conversion of C20:4 to prostanoids has been identified as central to cardioprotection during ischemic preconditioning (28) and resolution of pleural inflammation (29,30). COX-1-derived products may also have protective functions because its expression decreased after ALI, and deficiencies in COX-1 can exacerbate pulmonary inflammation in response to allergic and infectious stimuli (20,31).…”