Anti-IL-5 monoclonal antibody inhibits allergic late phase bronchial eosinophilia in guinea pigs: a therapeutic approach

Chand, N.; Je, Harrison; Rooney, Sean; Pillar, J.; Jakubicki, R. G.; Nolan, K.; Diamantis, W.; Rd, Sofia

doi:10.1016/0014-2999(92)90273-7

Cited by 103 publications

(48 citation statements)

References 9 publications

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“…The ovalbumin-sensitized guinea-pig model was selected, since it has been shown to demonstrate both early-and late-phase asthmatic reactions, as well as airway eosinophilia, and bronchial hyperreactivity. Studies were undertaken to assess factors responsible for development of airway eosinophilia [37,38]. Dunkin-Hartley guineapigs were sensitized by i.p.…”

Section: Guinea-pig Modelsmentioning

confidence: 99%

Animal models of occupational asthma

Mh¹

1994

Eur Respir J

122

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A An ni im ma al l m mo od de el ls s o of f o oc cc cu up pa at ti io on na al l a as st th hm ma a M.H. KarolAnimal models of occupational asthma. M.H. Karol. ERS Journals Ltd 1994. ABSTRACT: Occupational asthma is characterized by variable airflow obstruction occurring in the workplace. The presence of airways inflammation and hyperreactivity provides further evidence for the disease. Since its pathogenic mechanism(s) are unknown, animal models have been developed to investigate the various disease processes, as well as to enable study of environmental and genetic factors which may contribute to disease development.Numerous parameters can be measured in animal systems, including specific and total immunoglobulin E (IgE), pulmonary eosinophilia, diaphragm contractions and airflow muscle hypertrophy. It is recognized that no single factor is sufficient to lead to a conclusion of occupational asthma, but rather that a selected combination of parameters is most fitting. Animal species selected for study have included: mice, rats, guinea-pigs, rabbits, sheep, horses and nonhuman primates. A guinea-pig system has been utilized for more than 90 yrs and has contributed to the basic understanding of physiological and immunological processes involved in allergic respiratory sensitization. The benefits as well as the disadvantages to be derived from each of the animal systems have been enumerated in this review.Certain caveats must be recognized in using animal systems. Attention must always be given to identifying differences which exist between animal and human systems, including morphological, physiological and immunological factors. The extent of bronchus-associated lymphoid tissue (BALT) differs greatly among animal species and probably plays a major role in development of allergic responsiveness in animals. In using animal systems, it must be appreciated that animals are only surrogates. Results from such studies must be compared with information obtained from clinical evaluation in order to avoid faulty extrapolations. Prudent employment of animal models is expected to advance the recognition, treatment and prevention of occupationally-based asthma.

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Section: Guinea-pig Modelsmentioning

confidence: 99%

Animal models of occupational asthma

Mh¹

1994

Eur Respir J

122

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“…Wehave reported that IL-5 production by CD4+T cells of asthmatic patients is significantly enhanced compared to that of healthy controls (13). Several experimental asthma models revealed that administration of anti-IL-5 neutralizing antibody inhibited the recruitment of eosinophils into the lung and abrogated the late phase bronchoconstriction (14)(15)(16)(17), clearly indicating the essential role of IL-5 in the late phase asthmatic response. T cells producing IL-3, GM-CSF,and IL-5 were also demonstrated in the late phase cutaneous reaction of atopic dermatitis patients upon antigen challenge (18).…”

Section: Introductionmentioning

confidence: 97%

Transcriptional Regulation of IL-5 Gene by Nontransformed Human T Cells Through the Proximal Promoter Element.

et al. 2000

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Objective IL-5 is strongly involved in the eosinophilic inflammation in bronchial asthma and atopic dermatitis. Wehave previously reported that IL-5 synthesis in atopic and nonatopic asthmatics is significantly enhanced compared to control subjects. T cell IL-5 synthesis is regulated through several transcriptional elements, one of which is the proximal human IL-5 promoter (-62 to -46). The present study was undertaken to delineate the transcriptional regulation through this element using nontransformed human T cells. Methods Con A blast lymphocytes which tolerate electroporation were derived from peripheral blood lymphocytes. Luciferase reporter analysis and gel shift analysis were performed. Results The proximal promoter element is the overlapping binding site for the constitutive binding factor, Oct-1, and the inducible one, AP-1. The transcriptional induction was ascribed to the inducible binding, while the constitutive binding was rather inhibitory. A mutant element which lost the constitutive binding but retained the inducible binding exerted 3 times more transcriptional activity compared to the wild type element. In contrast, another mutant element which lost the inducible binding and retained the constitutive binding exhibited no transcriptional induction. Gel shift analysis clarified that the inducible binding was more prominent and the constitutive binding was less in IL-5-producing T cells derived from asthma patients compared to IL-5-nonproducing cells derived from control subjects. Conclusions The ratio of the inducible/constitutive binding to the proximal promoter element maydetermine the capacity of human Th cells to transcribe IL-5 gene, and its regulation may control eosinophilic inflammation. (Internal Medicine 39: 618-625, 2000)

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“…Eosinophils play an important role in the chronic inflammation and pathology of the bronchial mucosa seen in asthma (4). IL-5 has been strongly implicated as a major factor controlling the local infiltration and activation of eosinophils in this disease (5)(6)(7).…”

Section: Interleukin-5 (Il-5)mentioning

confidence: 99%