Detection of interleukin-5 messenger RNA and interleukin-5 protein in bronchial biopsies from asthma by nonradioactive in situ hybridization and immunohistochemistry

Fukuda, Takeshi; Nakajima, Hirokazu; Fukushima, Yasutsugu; Akutsu, I; Numao, Toshio; Majima, Keiko; Motojima, Seiji; Sato, Yuichi; Takatsu, Kiyoshi; Makino, Sohei

doi:10.1016/0091-6749(94)90134-1

Cited by 17 publications

(6 citation statements)

References 30 publications

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“…Atopic asthmatic persons have increased expression of Th2-type cytokine (interleukin-2, interleukin-3, interleukin-4, interleukin-5, and GM-CSF) mRNA in both BAL fluid and in bronchial biopsies as compared with healthy volunteers, but there is no difference between the two groups in the expression of Th1-type cytokine mRNA such as interferon-γ [82,83,84,85]. The predominant source of interleukin-4 and interleukin-5 mRNA in asthmatic persons is the T lymphocyte, and the CD4 + and CD8 + T-cell populations express elevated levels of activation markers including interleukin-2 receptor (CD25), human leukocyte antigen-DR, and the very late activation antigen-1 [84,86,87,88,89,90].…”

Section: Interleukin-5 In Human Asthmamentioning

confidence: 99%

Th2 cytokines and asthma The role of interleukin-5 in allergic eosinophilic disease

Greenfeder¹,

Umland²,

Cuss³

et al. 2001

Respir Res

207

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Available online http://respiratory-research.com/content/2/2/071 IntroductionSeveral allergic diseases, such as nasal rhinitis, nasal polyps, asthma, idiopathic eosinophilic syndromes, and atopic dermatitis, have prominent inflammatory components that are characterized by pronounced eosinophilic infiltration [1]. As a result, the role of chronic pulmonary inflammation in the pathophysiology of asthma has been studied extensively in human and in animal models. In asthma, pulmonary inflammation is characterized by edema, decreased mucociliary clearance, epithelial damage, increased neuronal responsiveness, and bronchoalveolar eosinophilia [1].Eosinophils form in the bone marrow from myeloid precursors in response to cytokine activation, and are released into the circulation following an appropriate stimulus [2]. Once in the circulation they accumulate rapidly in tissue, where they synthesize and release lipid mediators that can cause edema, bronchoconstriction and chemotaxis, and secrete enzymes and proteins that can damage tissue [2].The eosinophil is therefore an ideal target for selectively inhibiting the tissue damage that accompanies allergic diseases, without inducing the immunosuppressive consequences that can arise from systemic use of pleiotropic drugs such as steroids.Interleukin-5 acts as a homodimer, and is essential for maturation of eosinophils in the bone marrow and their release into the blood [3][4][5][6]. In humans, interleukin-5 acts only on eosinophils and basophils, in which it causes maturation, growth, activation, and survival [7,8]. This specificity occurs because only those cells possess the interleukin-5 receptor. The functional high-affinity interleukin-5 receptor (250 pmol/l) is composed of two subunits: an α-subunit that is unique to interleukin-5, and a β c -subunit that is shared with interleukin-3 and granulocyte macrophage-colony stimulating factor (GM-CSF) [9,10].In animals and in humans, inhibiting interleukin-5 with monoclonal antibodies can reduce blood and bronchoReview Th2 cytokines and asthma The role of interleukin-5 in allergic eosinophilic disease AbstractInterleukin-5 is produced by a number of cell types, and is responsible for the maturation and release of eosinophils in the bone marrow. In humans, interleukin-5 is a very selective cytokine as a result of the restricted expression of the interleukin-5 receptor on eosinophils and basophils. Eosinophils are a prominent feature in the pulmonary inflammation that is associated with allergic airway diseases, suggesting that inhibition of interleukin-5 is a viable treatment. The present review addresses the data that relate interleukin-5 to pulmonary inflammation and function in animal models, and the use of neutralizing anti-interleukin-5 monoclonal antibodies for the treatment of asthma in humans. [11][12][13][14]. Therefore, exclusively inhibiting the actions of interleukin-5 can suppress at least one of the alleged causes of asthma, namely tissue damage due to eosinophil accumulation during pulmonary inflammation.Altho...

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Section: Interleukin-5 In Human Asthmamentioning

confidence: 99%

Th2 cytokines and asthma The role of interleukin-5 in allergic eosinophilic disease

Greenfeder¹,

Umland²,

Cuss³

et al. 2001

Respir Res

207

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“…[14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] Furthermore, mast cells are not only associated with effector mechanisms, whether immediate or delayed, but might also participate in earlier phases of the allergic reaction, like the sensitization phase, through the release of immunoregulatory cytokines. 18,23 Most data linking mast cells to IgE-mediated conditions come from studies performed in human systems [29][30][31][32][33][34][35][36][37][38][39] and rodents, [40][41][42][43][44][45] where very useful in vivo models have been established. [46][47][48][49][50][51][52] In addition, studies of human and animal mast cell cultures have made significant contributions to our understanding of the pathogenesis of atopic diseases.…”

mentioning

confidence: 99%

“…Most data linking mast cells to IgE‐mediated conditions come from studies performed in human systems 29–39 and rodents, 40–45 where very useful in vivo models have been established 46–52 . In addition, studies of human and animal mast cell cultures have made significant contributions to our understanding of the pathogenesis of atopic diseases 53–57 .…”

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confidence: 99%

The role of mast cells in atopy: what can we learn from canine models? A thorough review of the biology of mast cells in canine and human systems

Mora

Puigdemont

Torres

2006

British Journal of Dermatology

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Mast cell research has largely focused on the role of these cells in the early phase of allergic reactions. However, their involvement may well extend beyond this stage, and even reach across nonallergic conditions. Mast cells from different sources have helped advance our knowledge of their biology. Although in vitro and in vivo research in this area has mainly focused on humans, such studies are limited by the extent to which cells from certain human tissues and/or human patients can be collected or studied. While rodents also provide valuable models with which to further our understanding of the behaviour of mast cells and their contribution to allergy, reported differences between human and murine mast cells, and, in some instances, the limitations of in vivo rodent models of mast cell-mediated allergic conditions, preclude their use. In this review, we introduce a relatively unknown mast cell population, that of the dog. Canine mast cells display many phenotypic and functional similarities with their human counterparts, and dogs develop spontaneous and induced allergic diseases that share clinical and pathophysiological features with the human condition. Therefore, the use of canine cells can shed light on the general role of mast cells, particularly in relation to allergic diseases given the potential of in vivo dog models within this field. Here we provide a detailed review of the data reported from in vitro and in vivo studies of canine mast cells, and compare them with results obtained in human systems. We also highlight direct evidence of the mast cell contribution to canine atopy. We conclude that the dog offers useful in vitro and in vivo models in which to investigate mast cell behaviour, and that its use should be considered when undertaking studies aimed either at elucidating the role of mast cells in health and disease, or at prescreening novel therapies prior to entry into man.

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“…Although the validity of the Th1/Th2 classification to the human situation has generated much debate, it is becoming clear that there is an increase in the numbers of cells expressing mRNA for IL‐4 and IL‐5, but not IFN‐γ, in the airways of human allergic asthmatics after an antigen challenge and in symptomatic asthmatics when compared with asymptomatic controls (Robinson et al , 1993b, d). Furthermore, biopsy studies have revealed increased expression of mRNA for IL‐5 in the bronchial mucosa of human asthmatics compared with that of non‐asthmatic controls (Hamid et al , 1991; Fukuda et al , 1994). Bronchial lavage fluid from human asthmatics contains a higher concentration of IL‐4 and IL‐5, but not IFN‐γ, than that from non‐asthmatic controls, demonstrating that increased IL‐4 and IL‐5 gene expression does lead to increased protein synthesis (Walker et al , 1994).…”

Section: Discussionmentioning

confidence: 99%

RPR 106541, a novel, airways‐selective glucocorticoid: effects against antigen‐induced CD4⁺T lymphocyte accumulation and cytokine gene expression in the Brown Norway rat lung

Underwood¹,

Raeburn²,

Lawrence³

et al. 1997

British J Pharmacology

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The effects of a novel 17‐thiosteroid, RPR 106541, were investigated in a rat model of allergic airway inflammation. In sensitized Brown Norway rats, challenge with inhaled antigen (ovalbumin) caused an influx of eosinophils and neutrophils into the lung tissue and airway lumen. In the lung tissue there was also an accumulation of CD4+ T lymphocytes and increased expression of mRNA for interleukin‐4 (IL‐4) and IL‐5, but not interferon‐γ (IFN‐γ). These findings are consistent with an eosinophilia orchestrated by activated Th2‐type cells. RPR 106541 (10–300 μg kg−1), administered by intratracheal instillation into the airways 24 h and 1 h before antigen challenge, dose‐dependently inhibited cell influx into the airway lumen. RPR 106541 (100 μg kg−1) caused a significant (P<0.01) (98%) inhibition of eosinophil influx and a significant (P<0.01) (100%) inhibition of neutrophil influx. RPR 106541 was approximately 7 times and 4 times more potent than budesonide and fluticasone propionate, respectively. When tested at a single dose (300 μg kg−1), RPR 106541 and fluticasone each caused a significant (P<0.01) (100%) inhibition of CD4+ T cell accumulation in lung tissue. Budesonide (300 μg kg−1) had no significant effect. RPR 106541 and fluticasone (300 μg kg−1), but not budesonide (300 μg kg−1), significantly (P<0.05) inhibited the expression within lung tissue of mRNA for IL‐4. RPR 106541 (300 μg kg−1) also significantly (P<0.05) inhibited expression of mRNA for IL‐5. The high topical potency of RPR 106541 in this model, which mimics important aspects of airway inflammation in human allergic asthmatics, suggests that this glucocorticoid may be useful in the treatment of bronchial asthma. British Journal of Pharmacology (1997) 122, 439–446; doi:

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Detection of interleukin-5 messenger RNA and interleukin-5 protein in bronchial biopsies from asthma by nonradioactive in situ hybridization and immunohistochemistry

Cited by 17 publications

References 30 publications

Th2 cytokines and asthma The role of interleukin-5 in allergic eosinophilic disease

Th2 cytokines and asthma The role of interleukin-5 in allergic eosinophilic disease

The role of mast cells in atopy: what can we learn from canine models? A thorough review of the biology of mast cells in canine and human systems

RPR 106541, a novel, airways‐selective glucocorticoid: effects against antigen‐induced CD4⁺T lymphocyte accumulation and cytokine gene expression in the Brown Norway rat lung

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Detection of interleukin-5 messenger RNA and interleukin-5 protein in bronchial biopsies from asthma by nonradioactive in situ hybridization and immunohistochemistry

Cited by 17 publications

References 30 publications

Th2 cytokines and asthma The role of interleukin-5 in allergic eosinophilic disease

Th2 cytokines and asthma The role of interleukin-5 in allergic eosinophilic disease

The role of mast cells in atopy: what can we learn from canine models? A thorough review of the biology of mast cells in canine and human systems

RPR 106541, a novel, airways‐selective glucocorticoid: effects against antigen‐induced CD4+T lymphocyte accumulation and cytokine gene expression in the Brown Norway rat lung

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Product

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RPR 106541, a novel, airways‐selective glucocorticoid: effects against antigen‐induced CD4⁺T lymphocyte accumulation and cytokine gene expression in the Brown Norway rat lung