The effects of nebulized recombinant interferon-γ in asthmatic airways

Boguniewicz, Mark; Martin, Richard J.; Martín, David Rentero; Gibson, Ursula E. M.; Celniker, Abbie; Williams, Mickey; Leung, Donald Y.M.

doi:10.1016/s0091-6749(95)70162-1

Cited by 109 publications

(50 citation statements)

References 6 publications

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“…To date, however, exogenous administration of IFN-c in humans has proven disappointing. Nebulized IFN-c was reported not to influence baseline FEV1 in mild asthma, and subcutaneous administration of IFN-c did not offer any improvement in steroid-dependent asthmatics [101,102].…”

Section: Immunomodulatory Cytokinesmentioning

confidence: 89%

Cytokines in asthma

2001

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The airway inflammation underlying asthma is regulated by a network of mutually interacting cytokines. The exact functional role of each individual cytokine in the pathogenesis of the disease remains to be fully established.Type 2 T-helper cells are currently considered to play a crucial role in this process. In vivo animal data suggest a sequential involvement of interleukin (IL)-4 and IL-5 in the induction of allergen-induced airway changes. The potential role of other type 2 T-helper cell-like cytokines in asthma is increasingly being recognized. In particular, IL-4 and -13 display a large degree of redundancy. Whereas IL-4 seems to be crucial in the primary allergen sensitization process, IL-13 might be more important during secondary exposure to aerosolized allergen. Animal models also indicate that T-cellderived cytokine production, rather than eosinophil influx or immunoglobulin-E synthesis, is causally related to altered airway behaviour.An important aspect when evaluating the functional role of cytokines in a complex disease such as asthma is the interaction with other cytokines in the microenvironment. Increased expression of pro-inflammatory cytokines such as tumour necrosis factor-a can further enhance the inflammatory process, and is increasingly linked to disease severity. In addition, decreased expression of immunoregulatory cytokines, including interleukin-12, interleukin-18 or interferon gamma could also strengthen the type 2 T-helper cell-driven inflammatory process.

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Section: Immunomodulatory Cytokinesmentioning

confidence: 89%

Cytokines in asthma

2001

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“…Targeted disruption of the IFN-γ receptor gene has resulted in a prolonged airway eosinophilia in response to allergen, suggesting that IFN-γ signaling pathway is crucial to control eosinophil recruitment in vivo (Coyle et al 1996). In human studies, nebulized IFN-γ has also reduced the number of eosinophils in the BAL of asthmatic patients (Boguniewicz et al 1995). However, it is unlikely that this cytokine directly acts on the eosinophils during its infiltration to inflammatory tissues.…”

Section: Ifn-γ γ γ γ γ and Allergic Inflammationmentioning

confidence: 97%

The role of interferon-gamma on immune and allergic responses

Teixeira

Fonseca

Barboza

et al. 2005

Mem. Inst. Oswaldo Cruz

117

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“…Small molecule inhibitors of pathways downstream of EGFR and IL-13, including inhibitors of MEK, p38 mitogen-activated protein kinase, and PI3K are other potential pathways whereby specific blockade might impact on mucus hypersecretion. Inhaled IFN-g has been tested in subjects with asthma over a short period of exposure (80), but never tested for its long-term efficacy in asthma or mucus hypersecretion.…”

Section: Anti-inflammatory Therapiesmentioning

confidence: 99%

Advances in Mucous Cell Metaplasia

Curran

Cohn

2010

Am J Respir Cell Mol Biol

164

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Mucous cell metaplasia is induced in response to harmful insults and provides front-line protection to clear the airway of toxic substances and cellular debris. In chronic airway diseases mucous metaplasia persists and results in airway obstruction and contributes significantly to morbidity and mortality. Mucus hypersecretion involves increased expression of mucin genes, and increased mucin production and release. The past decade has seen significant advances in our understanding of the molecular mechanisms by which these events occur. Inflammation stimulates epidermal growth factor receptor activation and IL-13 to induce both Clara and ciliated cells to transition into goblet cells through the coordinated actions of FoxA2, TTF-1, SPDEF, and GABA A R. Ultimately, these steps lead to up-regulation of MUC5AC expression, and increased mucin in goblet cell granules that fuse to the plasma membrane through actions of MARCKS, SNAREs, and Munc proteins. Blockade of mucus in exacerbations of asthma and chronic obstructive pulmonary disease may affect morbidity. Development of new therapies to target mucus production and secretion are now possible given the advances in our understanding of molecular mechanisms of mucous metaplasia. We now have a greater incentive to focus on inhibition of mucus as a therapy for chronic airway diseases.

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The effects of nebulized recombinant interferon-γ in asthmatic airways

Cited by 109 publications

References 6 publications

Cytokines in asthma

Cytokines in asthma

The role of interferon-gamma on immune and allergic responses

Advances in Mucous Cell Metaplasia

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