Involvement of IL-5 in a murine model of allergic pulmonary inflammation: prophylactic and therapeutic effect of an anti-IL-5 antibody.

Kung, Ted T.; Stelts, Dawn; Zurcher, Jackie; Adams, G. K.; Egan, Robert W.; Kreutner, William; Watnick, Arthur S.; Jones, Howard; Chapman, Richard W.

doi:10.1165/ajrcmb.13.3.7654390

Cited by 187 publications

(111 citation statements)

References 29 publications

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“…It is possible that increased serum level of IL-5 may originate from several tissues, including lungs, local lymph nodes, and bone marrow. However, the exact site of action of anti-IL-5 on allergen-induced airway eosinophilia has not been clearly described in several previous studies in which anti-IL-5 was administered systemically (27)(28)(29)(30)(31)(32). A recent study has shown that the anti-IL-5 Ab delivered via the airway route attenuates allergen-induced eosinophilia in BAL and lung tissues (47).…”

Section: Discussionmentioning

confidence: 99%

Eosinophilopoiesis in A Murine Model of Allergic Airway Eosinophilia: Involvement of Bone Marrow IL-5 and IL-5 Receptor α

Tomaki

Zhao

Lundahl

et al. 2000

The Journal of Immunology

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The airway inflammation in asthma is dominated by eosinophils. The aim of this study was to elucidate the contribution of newly produced eosinophils in airway allergic inflammation and to determine mechanisms of any enhanced eosinophilopoiesis. OVA-sensitized BALB/c mice were repeatedly exposed to allergen via airway route. Newly produced cells were identified using a thymidine analog, 5-bromo-2′-deoxyuridine, which is incorporated into DNA during mitosis. Identification of IL-5-producing cells in the bone marrow was performed using FACS. Bone marrow CD3+ cells were enriched to evaluate IL-5-protein release in vitro. Anti-IL-5-treatment (TRFK-5) was given either systemically or directly to the airways. IL-5R-bearing cells were localized by immunocytochemistry. Repeated airway allergen exposure caused prominent airway eosinophilia after three to five exposures, and increased the number of immature eosinophils in the bone marrow. Up to 78% of bronchoalveolar lavage (BAL) granulocytes were 5-bromo-2′-deoxyuridine positive. After three allergen exposures, both CD3+ and non-CD3 cells acquired from the bone marrow expressed and released IL-5-protein. Anti-IL-5 given i.p. inhibited both bone marrow and airway eosinophilia. Intranasal administration of anti-IL-5 also reduced BAL eosinophilia, partly via local effects in the airways. Bone marrow cells, but not BAL eosinophils, displayed stainable amounts of the IL-5R α-chain. We conclude that the bone marrow is activated by airway allergen exposure, and that newly produced eosinophils contribute to a substantial degree to the airway eosinophilia induced by allergen. Airway allergen exposure increases the number of cells expressing IL-5-protein in the bone marrow. The bone marrow, as well as the lung, are possible targets for anti-IL-5-treatment.

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Section: Discussionmentioning

confidence: 99%

Eosinophilopoiesis in A Murine Model of Allergic Airway Eosinophilia: Involvement of Bone Marrow IL-5 and IL-5 Receptor α

Tomaki

Zhao

Lundahl

et al. 2000

The Journal of Immunology

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“…Some investigators have suggested that AHR may be dependent on IL-4, which plays a major role in the induction of an IgE response, or on IgE itself (Brusselle et al, 1995;Corry et al, 1996;Hamelmann et al, 1997b). Several reports also indicate that IL-5, which regulates accumulation of eosinophils, plays an important role in AHR and the pathophysiology of changes in the respiratory epithelium (Foster et al, 1996;Hogan et al, 1997a;1998a;Kung et al, 1995;Nakajima et al, 1992).…”

mentioning

confidence: 99%

Dissociation of Inflammatory and Epithelial Responses in a Murine Model of Chronic Asthma

Foster

Yang

Matthei

et al. 2000

Laboratory Investigation

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SUMMARY:To study pathogenetic mechanisms in chronic asthma, we employed a novel experimental model that replicates characteristic features of the human disease. Chronic inflammation and epithelial changes, specifically localized to the airways, were induced by repeated exposure of systemically sensitized BALB/c mice to low mass concentrations of aerosolized ovalbumin for 6 weeks. The contribution of Th2 cytokine-driven inflammation to the development of airway lesions and hyperreactivity was assessed in cytokine-deficient mice. In interleukin-5-deficient animals, intraepithelial eosinophils and chronic inflammatory cells in the lamina propria of the airways were markedly decreased; however, these animals developed epithelial hypertrophy and subepithelial fibrosis comparable with that observed in sensitized wild type mice. Airway hyperreactivity to inhaled methacholine did not develop in interleukin-5-deficient mice. In contrast, interleukin-4-deficient mice exhibited no decrease in airway inflammation, but had significantly greater epithelial hypertrophy and subepithelial fibrosis, as well as exaggerated hyperreactivity to methacholine. We conclude that interleukin-5, but not interleukin-4, plays a central role in the development of chronic inflammation of the airways and the induction of airway hyperreactivity. Furthermore, chronic epithelial and fibrotic changes occur independently of interleukin-5 and are not required for the development of airway hyperreactivity. The dissociation between airway wall remodeling and airway hyperreactivity has important implications for therapeutic approaches to chronic asthma. (Lab Invest 2000, 80:655-662).

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“…Therefore, inhibition of IL-5 activity during established pulmonary eosinophilia could cause tissue damage by destruction of eosinophils and release of their inflammatory mediators. However, studies in allergic mice have shown that administration of an antibody to IL-5 after antigen challenge, when lung eosinophilia was already established, did not increase tissue damage in the lungs (97). These results have important therapeutic implications for the potential use of IL-5 inhibitors in the treatment of inflammatory airway disorders.…”

Section: Animal Models Of Asthmamentioning

confidence: 94%

“…It is important to note that mast cells are much less important in the development of pulmonary eosinophilia after a multiple antigen challenge paradigm in mice (96). Recent studies in allergic mice suggest that IL-5 is also important for the migration of eosinophils from the bone marrow into the blood and lungs because treatment of mice with a monoclonal antibody to IL-5 blocked the decrease in bone marrow eosinophils as they migrate from the bone marrow into the blood and lungs after provocation with allergen (97,98).…”

Section: Animal Models Of Asthmamentioning

confidence: 99%

Biology of interleukin-5 and its relevance to allergic disease

Egan¹,

Umland²,

Cuss³

et al. 1996

Allergy

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Involvement of IL-5 in a murine model of allergic pulmonary inflammation: prophylactic and therapeutic effect of an anti-IL-5 antibody.

Cited by 187 publications

References 29 publications

Eosinophilopoiesis in A Murine Model of Allergic Airway Eosinophilia: Involvement of Bone Marrow IL-5 and IL-5 Receptor α

Eosinophilopoiesis in A Murine Model of Allergic Airway Eosinophilia: Involvement of Bone Marrow IL-5 and IL-5 Receptor α

Dissociation of Inflammatory and Epithelial Responses in a Murine Model of Chronic Asthma

Biology of interleukin-5 and its relevance to allergic disease

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