Eosinophil function in health and disease☆

Asthma is a syndrome of variable airflow obstruction. It is characterized pathologically by bronchial inflammation and remodeling changes. Eosinophil infiltrate in asthma and a relationship between the degree of eosinophil infiltration in airways and severity of asthma has been suggested. Eosinophil has antigen-presenting cells and main role in allergic asthma. Platelets in inflammatory response is very important. It has also been shown that enzymes released by activated platelets play a direct role in the chronic inflammatory events that lead to airway remodeling in asthma. Dendritic cells (DCs) acquire antigen in the airways and then migrate to the draining lymph node where the cells mature and initiate T cell responses. Allergen challenge induces simultaneous increases in the number of DCs in the lungs. Because DCs are crucial in mounting immune responses during ongoing inflammation in the lung and balance of the allergic immune response.

Prominent eosinophil infiltration is a characteristic of some forms of vasculitis, such as Churg-Strauss syndrome, also known as allergic granulomatous vasculitis. In the current study, we established a mouse model of cutaneous eosinophilic vasculitis by the cutaneous reverse passive Arthus reaction using IgE injection instead of IgG. Wild-type C57BL/6 mice were injected with IgE anti-trinitrophenyl antibodies, followed immediately by intravenous administration of trinitrophenyl bovine serum albumin. IgE-mediated immune complex challenge induced substantial hemorrhage with marked infiltration of eosinophils in which neutrophils, mast cells, and macrophages were also mixed. This finding contrasted remarkably with the neutrophil-dominant infiltration pattern in IgG-mediated immune complex challenge. In the lesion, the expression level of monocyte chemotactic protein-3 was increased, and anti-monocyte chemotactic protein-3 treatment resulted in a significant but incomplete blockade of eosinophil recruitment. Furthermore, mice lacking E-selectin, P-selectin, L-selectin, or intercellular adhesion molecule-1, as well as wild-type mice that received anti-vascular cell adhesion molecule-1-blocking antibodies were assessed for the IgE-mediated Arthus reaction. After 24 hours, the loss of P-selectin resulted in a significant reduction in eosinophil accumulation compared with both wild-type mice and other mouse mutants. Collectively, the Fc class of immunoglobulins, which forms these immune complexes, critically determines the disease manifestation of vasculitis. The IgE-mediated cutaneous reverse passive Arthus reaction may serve as an experimental model for cutaneous eosinophilic infiltration in vasculitis as well as in other diseases.

Allergic rhinitis affects 10-30% of the population, negatively impacting one's quality of life and productivity. It has been associated with sinusitis, otitis media, sleep disorders, and asthma. Rupatadine is a second generation antihistamine with increased affinity to histamine receptor H1; it is also a potent PAF (platelet-activating factor) antagonist. It starts acting quite quickly, offers long lasting effect, and reduces the chronic effects of rhinitis.

this study aims to assess the efficacy and safety of rupatadine in the treatment of persistent allergic rhinitis.

this is a multi-centric open prospective study. This study included 241 patients from 13 centers in Brazil and was held between October of 2004 and August of 2005. Signs and symptoms of rhinitis and tolerance to medication were analyzed after one and two weeks of treatment.

reduction on general scores from 8.65 to 3.21 on week 2 (p<0.001). All signs and symptoms improved significantly in the first day of treatment (p<0.001), except for nasal congestion and secretion, which improved from the second day of treatment (p<0.001). Adverse events occurred in 19.9% of the cases, 27.7% on week 1.

rupatadine effectively controls persistent allergic rhinitis; it is safe and presents low incidence of side effects.

The pathogenesis of otitis media with effusion (OME) is considered multifactorial, with viral upper respiratory tract infection and eustachian tube dysfunction. Allergy may be related to the pathogenesis of OME or to another etiological factor. We investigated the role of allergic rhinitis (AR) in children with OME and evaluated eustachian tube function in patients with AR.

We prospectively analyzed the prevalence of AR, serum eosinophil count, and serum total IgE concentrations in 123 children with OME and in 141 controls. IgE concentration in middle ear effusion was compared in children with OME with and without AR, and eustachian tube function after a nasal provocation test was compared between patients with AR and controls.

The prevalence of AR in children with OME (28.4%) and control subjects (24.1%) did not differ significantly. These 2 groups also showed no differences in total eosinophil count and serum and middle ear effusion IgE concentration. Abnormalities in eustachian tube function were the same in patients with AR and controls.

Allergic rhinitis may not be related to the development of OME in children.

This chapter focuses on essential concepts that are of particular relevance for the design of immunotoxicity studies and the interpretation of results. The immune system is an extremely complex array of cells and mediators that interact to mount immune responses, which can be either beneficial or detrimental. Because of this complexity, it is recommended that immunotoxicity evaluation is not based on trivial or isolated end-points that cannot reflect the whole spectrum of mechanisms possibly involved. From the viewpoint of a toxicologist, a major limitation of current research and teaching in immunology is that a global approach of the immune system and immune responsiveness is seldom, if ever proposed, an opinion that is shared by few but prominent immunologists In any case, one single change cannot be considered as equal to immunotoxicity but instead should be included in a wider perspective. Establishing the relevance of changes in the morphology of the lymphoid tissue or immune function may, therefore, require the use of global—host resistance—models.