Airways inflammation is thought to play a central role in the pathogenesis of asthma. However, the precise role that individual inflammatory cells and mediators play in the development of airways hyperreactivity and the morphological changes of the lung during allergic pulmonary inflammation is unknown. In this investigation we have used a mouse model of allergic pulmonary inflammation and interleukin (IL) 5-deficient mice to establish the essential role of this cytokine and eosinophils in the initiation of aeroallergen-induced lung damage and the development of airways hyperreactivity. Sensitization and aerosol challenge of mice with ovalbumin results in airways eosinophilia and extensive lung damage analogous to that seen in asthma. Aeroallergen-challenged mice also display airways hyperreactivity to beta-methacholine. In IL-5-deficient mice, the eosinophilia, lung damage, and airways hyperreactivity normally resulting from aeroallergen challenge were abolished. Reconstitution of IL-5 production with recombinant vaccinia viruses engineered to express this factor completely restored aeroallergen-induced eosinophilia and airways dysfunction. These results indicate that IL-5 and eosinophils are central mediators in the pathogenesis of allergic lung disease.

/pdf/interleukin-5-deficiency-abolishes-eosinophilia-airways-2tadb7e4r5.pdf

Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model.

During the annual meeting in Glasgow, July 1990, the Executive Committee of the European Academy of Allergology and Clinical Immunology (EAACI) decided to transform the Subcommittee on Skin Tests to the Subcommittee on Allergen Standardization and Skin Tests. Furthermore, the business meeting of this Subcommittee decided to produce a revised version of the 1989 Position Paper on skin tests used in type I allergy skin testing and include in the new version a chapter on “Allergen standardization by in vitro and in vivo methods”, replacing the chapter on “Biologic standardization”. The new chapter includes a general description of factors which affect the potency and composition of allergen extracts and a second part focusing on standardization of allergenic extracts used for skin testing. The subcommittees on immunotherapy, provocation tests, and in vitro tests are responsible for preparing position papers on the Academy’s view on standardization of allergens for immunotherapy, in vivo provocation tests, and in vitro tests, respectively. When outlining Chapter4, we have been in contact with these subcommittees. This position paper does not cover skin tests used for the study of immune complex diseases and delayed-type hypersensitivity. The different chapters of the position paper on Allergen standardization and skin tests have been worked out by members of the Steering Committee of the Subcommittee on Allergen Standardization and Skin Tests. Draft chapters were circulated to all members and other interested parties and were discussed during a special session at the annual meeting in Zurich in May 1991. The final version was discussed and approved by the subcommittee and then by the EAACI Executive Committee during the Congress held in Paris in May 1992. During recent years, methods and goals for allergen standardization have been the subject of intense discussions within the Academy, and among authorities and industries, and, recently, the EC regulatory authority has approved directives and guidelines for registration of allergenic preparations in Europe. These directives and guidelines will soon be implemented by member countries. There is an international system for allergen standardization and a number of WHO/IUIS International Standards (IS), labeled in arbitrary International Units (IU). The Academy stresses the importance of assessing the potency of allergenic preparations, intended for all types of use, in IU, giving the method for calibration of potency against these IS, in order to allow comparison of different materials used in scientific investigations and to give an idea of the difference in potency between materials prepared by different manufacturers. The Academy also promotes the use of biologically relevant units suitable for labeling commercially available extracts used for diagnosis, since such units allow better and more reliable diagnosis of sensitization and atopic disease. A number of company-specific units have been launched: some of these units are equivalent to units prescribed by authorities; that is, the Nordic Biological Unit (BU/ml) and the US Allergy Unit (AU/ ml). Other units are less well documented. For scientific purposes, it is essential that wellstandardized extracts or pure allergenic components of such extracts be used. Methods of skin testing vary among regions and also among medical specialties. At present, the skin prick test method using a lancet with 1-mm tip is the method of choice for routine diagnosis, especially among pediatricians. In contrast to results obtained by laboratory methods, skin test results are often presented without giving any details of the potency of the allergen preparation used, the method of testing, or reproducibility in the hands of the investigator. This fact reduces the value of most published studies using skin tests. It is our hope that the recommendations in this position paper on the performance, evaluation, and use of skin tests in diagnosis, standardization, and epidemiologic studies, will be followed by European allergologists and, especially, by editors of scientific journals. Finally, we hope that this edition of the position paper will stimulate scientific work within the field. Sten Dreborg Anthony Frew July 1992

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1398-9995.1993.tb04756.x

Position Paper: Allergen standardization and skin tests

Inflammatory mediators of asthma: an update.

Asthma is estimated to affect 15 million people in the United States. After declining in the 1970s, its prevalence, morbidity, and mortality have increased since the 1980s. It now affects 1 in 7 children in the United Kingdom, and is the most frequent reason for preventable childhood hospitalizations in the United States. In 1990, total asthma-related health care costs were estimated at 6.2 billion dollars in the United States. This figure exceeded 10 billion dollars by 1995.

https://www.atsjournals.org/doi/pdf/10.1164/ajrccm.161.supplement_2.a1q4-4

Airway remodeling in asthma.

Reversible airway hyperreactivity underlies the pathophysiology of asthma, yet the precise mediators of the response remain unclear. Human studies have correlated aberrant activation of T helper (Th) 2-like effector systems in the airways with disease. A murine model of airway hyperreactivity in response to acetylcholine was established using mice immunized with ovalbumin and challenged with aerosolized antigen. No airway hyperractivity occurred in severe combined immunodeficient mice. Identically immunized BALB/c mice developed an influx of cells, with a predominance of eosinophils and CD4+ T cells, into the lungs and bronchoalveolar lavage fluid at the time that substantial changes in airway pressure and resistance were quantitated. Challenged animals developed marked increases in Th2 cytokine production, eosinophil influx, and serum immunoglobulin E levels. Neutralization of interleukin (IL) 4 using monoclonal antibodies administered during the period of systemic immunization abrogated airway hyperractivity but had little effect on the influx of eosinophils. Administration of anti-IL-4 only during the period of the aerosol challenge did not affect the subsequent response to acetylcholine. Finally, administration of anti-IL-5 antibodies at levels that suppressed eosinophils to < 1% of recruited cells had no effect on the subsequent airway responses. BALB/c mice had significantly greater airway responses than C57BL/6 mice, consistent with enhanced IL-4 responses to antigen in BALB/c mice. Taken together, these data implicate IL-4 generated during the period of lymphocyte priming with antigen in establishing the cascade of responses required to generate airway hyperractivity to inhaled antigen. No role for IL-5 or eosinophils could be demonstrated.

/pdf/interleukin-4-but-not-interleukin-5-or-eosinophils-is-13wra5yq65.pdf

Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway hyperreactivity.

We have attempted to identify mRNA for IL-5 in endobronchial mucosal biopsies from asthmatics and controls, using the technique of in situ hybridization. Bronchial biopsies were obtained from 10 asthmatics and 9 nonatopic normal controls. A radio-labeled cRNA probe was prepared from an IL-5 cDNA and hybridized to permeabilized sections. These were washed extensively before processing for autoradiography. An IL-5-producing T cell clone derived from a patient with the hyper-IgE syndrome was used as a positive control. As a negative control, sections were also treated with a \"sense\" IL-5 probe. Specific hybridization signals for IL-5 mRNA were demonstrated within the bronchial mucosa in 6 out of the 10 asthmatic subjects. Cells exhibiting hybridization signals were located beneath the epithelial basement membrane. In contrast, there was no hybridization in the control group. No hybridization was observed with the sense probe. The six IL-5 mRNA-positive asthmatics tended to have more severe disease than the negative asthmatics, as assessed by symptoms and lung function, and showed a significant increase in the degree of infiltration of the bronchial mucosa by secreting (EG2+) eosinophils and activated (CD25+) T lymphocytes. Within the subjects who showed positive IL-5 mRNA, there was a correlation between IL-5 mRNA expression and the number of CD25+ and EG2+ cells and total eosinophil count. This study provides evidence for the cellular localization of IL-5 mRNA in the bronchial mucosa of asthmatics and supports the concept that this cytokine regulates eosinophil function in bronchial asthma.

293 Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma

274 Localization of cells expressing mRNA for the cytokine gene cluster, IL-3, IL-4, IL-5 and GM-CSF in allergen-induced cutaneous late-phase reactions in atopic patients

R. Mogbel

Papers

293 Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma

274 Localization of cells expressing mRNA for the cytokine gene cluster, IL-3, IL-4, IL-5 and GM-CSF in allergen-induced cutaneous late-phase reactions in atopic patients