Characterization and pharmacological modulation of antigen-induced peritonitis in actively sensitized mice.
1. The intraperitoneal (i.p.) injection of 1 or 10 micrograms ovalbumin to sensitized Balb/c mice led to an acute histamine release, firstly evidenced 1 min after the challenge and returning to basal levels 30 min thereafter. This phenomenon was unaccompanied by protein extravasation. A dose-dependent increase in the amounts of immunoreactive leukotriene (LT) C4 and LTB4 was observed in the peritoneal washing from sensitized mice 6 h after 1 or 10 micrograms ovalbumin administration. In separate experiments, the i.p. administration of 1 mg activated zymosan to non-immunized mice was followed by a marked protein extravasation, and by immunoreactive LTC4 and LTB4, but not histamine, release in mouse peritoneum 1 h after its injection. 2. Mediator release in the mice peritoneal cavity was concomitant with a transient neutrophil infiltration, which peaked at 6 h and returned to basal levels therefore. An intense eosinophil accumulation starting at 24 h, peaking at 48 h and returning to basal values at 164 h, was also observed. 3. Ovalbumin (1 microgram)-induced eosinophilia, observed at 24 h, was reduced by the pretreatment of the animals with dexamethasone (1 mg kg-1, s.c.) or with the 5-lipoxygenase inhibitor, BWA4C (20 mg kg-1, s.c.), whereas indomethacin (2 mg kg-1, s.c.) and the platelet-activating factor (PAF)-antagonist SR 27417 (10 mg kg-1, s.c.) were ineffective. These results indicate that metabolites of arachidonic acid of lipoxygenase pathway, but not cyclo-oxygenase derivatives or PAF, mediate antigen-induced eosinophil accumulation in the mouse peritoneum. 4. The histamine HI receptor antagonist drug, cetirizine (15-30 mg kg-1, s.c.) markedly reduced ovalbumin-induced eosinophil accumulation under conditions where terfenadine was ineffective, suggesting that the effect of cetirizine was not related to the inhibition of the H1 receptor effects of histamine.5. The immunosuppressive agent, FK-506 (1-2 mg kg-1, s.c.) and the protein synthesis inhibitor,cylcoheximide, when administered either in situ (0.06 ng/cavity) or systemically (5 mg kg-1, s.c.),prevented antigen-induced eosinophil accumulation in the mouse peritoneum, contributing to the concept that substances (probably cytokines) originating from lymphocytes may be involved in the modulation of the eosinophilotactic response in this model.6. The results of the present study indicate that the i.p. administration of ovalbumin to actively sensitized mice induced late eosinophil accumulation in the peritoneal cavity. This phenomenon, which may be in part mediated by the release of lipoxygenase metabolites and/or by newly generated factors,such as T-lymphocytes-derived eosinophilotactic cytokines, offers an interesting tool to investigate the mechanism of action of anti-allergic and anti-inflammatory drugs.
Zuany-Amorim
C
C
Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur, INSERM n.285, Paris, France.
Leduc
D
D
Vargaftig
B B
BB
Pretolani
M
M
D000818:Animals; D044482:Benzeneacetamides; D017332:Cetirizine / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004804:Eosinophils / Q000276:immunology; D006636:Histamine Release / Q000187:drug effects; D006877:Hydroxamic Acids / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D007958:Leukocyte Count; D007975:Leukotriene B4 / Q000276:immunology / Q000378:metabolism; D017997:Leukotriene C4 / Q000276:immunology / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010529:Peritoneal Cavity / Q000166:cytology; D010538:Peritonitis / Q000188:drug therapy / Q000276:immunology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology; D016593:Terfenadine / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D015054:Zymosan
D044482:Benzeneacetamides; D006877:Hydroxamic Acids; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; D013844:Thiazoles; C056614:N-(3-phenoxycinnamyl)acetohydroxamic acid; D007975:Leukotriene B4; D017997:Leukotriene C4; D016593:Terfenadine; D003907:Dexamethasone; D010047:Ovalbumin; D015054:Zymosan; D003513:Cycloheximide; C071317:Foropafant; D016559:Tacrolimus; D007213:Indomethacin; D017332:Cetirizine