Differential effect of antiallergic drugs on IgE-mediated cutaneous reaction in passively sensitized mice.
We investigated the effect of several antiallergic agents on murine IgE-mediated biphasic cutaneous reaction. Mice were passively sensitized by an intravenous injection of monoclonal anti-dinitrophenol (anti-DNP) IgE antibody. Skin reaction was elicited by an epicutaneous challenge of dinitrofluorobenzene (DNFB) and occurred biphasically with immediate-phase response (IPR) and late-phase response (LPR) at 1 and 24 h, respectively. Classical histamine H1 receptor antagonists and some chemical mediator-release inhibitors, such as diphenhydramine and terfenadine, inhibited IPR, but not LPR. In contrast, leukotriene B(4) (LTB(4)) receptor antagonist (ONO-4057) inhibited LPR only. Antagonists for LTC(4), D(4), E(4) receptor (ONO-1078) and platelet-activating factor (PAF) receptor (Y-24180) significantly inhibited both IPR and LPR, similarly to prednisolone. We recently found that a third-phase inflammatory reaction with marked infiltration of eosinophils (named very-late-phase response; vLPR), which is supposed to be a more important reaction in allergic diseases, was induced, peaking at day 8 following IPR and LPR in this model. The effect of these drugs on the triphasic skin reaction can be scored based on efficacy against IPR / LPR / vLPR; +/+/+ (prednisolone, a PAF receptor antagonist Y-24180, cyclosporin A and FK-506), +/-/- (diphenhydramine), +/+/- (azelastine and LT receptor antagonist ONO-1078), and -/+/+ (an LTB(4) receptor antagonist ONO-4057). Thus the inhibitory effect on vLPR as well as LPR may relate to the inhibition of eosinophil function mediated by LTB(4) and PAF and/or T cells. These findings may provide the basis for a treatment modality using various antiallergic agents in allergic disease.
Satoh
T
T
Department of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
Tahara
E
E
Yamada
T
T
Watanabe
C
C
Itoh
T
T
Terasawa
K
K
Nagai
H
H
Saiki
I
I
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000276:immunology; D004139:Dinitrofluorobenzene / Q000276:immunology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007116:Immunization, Passive; D007073:Immunoglobulin E / Q000502:physiology*; D020024:Leukotriene Antagonists / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012882:Skin Tests
D018926:Anti-Allergic Agents; D000911:Antibodies, Monoclonal; D002867:Chromones; D006634:Histamine H1 Antagonists; D020024:Leukotriene Antagonists; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D007073:Immunoglobulin E; D004139:Dinitrofluorobenzene; C047681:pranlukast