Interleukin-5 involvement in ovalbumin-induced eosinophil infiltration in mouse food-allergy model.

A number of studies demonstrating the important role of interleukin-5 (IL-5) in eosinophil infiltration were reported. Antigen-induced eosinophil infiltrations to the trachea and skin were inhibited by pretreatment with monoclonal anti-IL-5 antibody. In this study, the role of IL-5 in eosinophil infiltration to the gut by oral challenge in mice is investigated. A marked eosinophil infiltration to the lamina propria was induced by oral challenge with ovalubumin (OVA) in Balb/c mice intraperitoneally sensitized with OVA, and peaked at 6 h after the oral challenge. Intraperitoneal preadministration of monoclonal anti-IL-5 antibody significantly decreased the eosinophil infiltration to the lamina propria. Furthermore, analysis by reverse transcription polymerase chain reaction (RT-PCR) demonstrated that IL-5 mRNA expression was induced in the lamina propria in an antigen-specific manner and the expression peaked at 6 h and declined thereafter. In-situ hybridization (ISH) revealed the presence of IL-5 mRNA positive cells at lesion site. As in bronchial mucosa and skin, IL-5 may play an important role in eosinophil recruitment to the lesion site in IgE mediated gut late phase reaction.

The inhibitory effect of anti-adhesion molecule antibodies on eosinophil infiltration in cutaneous late phase response in Balb/c mice sensitized with ovalbumin (OVA).

In this study, we investigated the involvement of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), very late activation antigen-4 (VLA-4), lymphocyte function-associated antigen 1 (LFA-1) and macrophage antigen-1 (Mac-1) on eosinophil infiltration in the cutaneous late phase response (LPR) in OVA-sensitized Balb/c mice by two approaches, immunostaining and inhibition assays with each monoclonal antibody. The eosinophil infiltration into the skin reached a peak at 12 hr after an intradermal challenge with OVA. Infiltrated eosinophils and mononuclear cells in the skin expressed Mac-1 (eosinophils: 38.9 +/- 1.55%, mononuclear cells: 51.2 +/- 2.15%), LFA-1 (eosinophils: 33.3 +/- 0.95%, mononuclear cells: 23.1 +/- 1.07%) and VLA-4 (eosinophils: 14.3 +/- 1.6%, mononuclear cells: 17.2 +/- 1.38%) at 12 h. Intraperitoneal administration of anti-mouse ICAM-1, VCAM-1, and VLA-4 monoclonal antibodies (mAb) before the challenge decreased the eosinophil infiltration by 66.2%, 61.0%, and 54.0%, respectively. On the other hand, pretreatment with anti-mouse LFA-1 mAb or Mac-1 mAb did not significantly decrease the infiltration. These results suggest that VCAM-1/VLA-4 interaction and ICAM-1 play important roles in eosinophil infiltration in cutaneous LPR.

[The inhibitory effect of LTB4 antagonist on eosinophil infiltration in cutaneous and gut late phase response in BALB/C mice sensitized with ovalubumin (OVA)].

In this study we investigated the effect of LTB4 antagonist on eosinophil infiltration in skin and gut late phase response (LPR) in OVA-sensitized BALB/c mice. The eosinophil infiltrations to skin and gut induced by skin and oral challenge reached a peak at 12 h and 6 h after the challenge, respectively. Intraperitoneal administration of LTB4 antagonist (ONO-4057) before the challenge significantly inhibited eosinophil infiltrations to the skin and gut by 53.3% and 73.7%, respectively (p < 0.05). Next, we investigated the effect to that by PAF antagonist (ONO-6240) and anti-IL-5 mAb in the skin system. OVA-induced eosinophil infiltration at 12 h after intracutaneous challenge was significantly inhibited by peritoneal administration of anti-IL-5 mAb before the challenge by 89.6% (p < 0.05), but not by that of PAF antagonist. Our results demonstrated the inhibitory effect of LTB4 antagonist on eosinophil infiltration in skin and gut LPR, suggesting the potency of LTB4 antagonist for treatment of skin lesion and food allergy in atopic dermatitis considered to be associated with LPR.