Antibodies directed against nerve growth factor inhibit the acute bronchoconstriction due to allergen challenge in guinea‐pigs

Vries, Annick de; Engels, Ferdi; Henricks, Paul A.J.; Leusink-Muis, Thea; Fischer, Axel; Nijkamp, Frans P.

doi:10.1046/j.1365-2222.2002.01283.x

Cited by 34 publications

(20 citation statements)

References 31 publications

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“…Local treatment with anti-NGF antibodies inhibited broncho-obstruction in a murine asthma model, whereas pulmonary NGF overexpression increased broncho-obstruction after allergen provocation [38]. Similar effects were observed in studies with guineapigs and rats [42,43]. The enhancement of acute airway obstruction by NGF might be due to its mast cell stimulatory function, indicated by the observed elevated serotonin levels in BALF of NGF-overexpressing mice [38].…”

Section: Neurotrophins and Earsupporting

confidence: 66%

The contribution of neurotrophins to the pathogenesis of allergic asthma

Rochlitzer

Nassenstein

Braun

2006

Biochemical Society Transactions

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The nature of persistent airway hyperreactivity and chronic inflammation in asthma remains unclear. It has been suggested that bi-directional neuro-immune interaction plays an important role in the pathogenesis of this disease, leading to enhanced airway narrowing after contact with unspecific stimuli, as well as infiltration, activation and degranulation of several immune cell subtypes. Important mediators in neuro-immune cross-talk are neurotrophins, which are produced by cells at the site of inflammation. In addition to modulating the function of several leucocyte subsets, they play an important role in the synthesis of neuropeptides by sensory nerve cells. Neuropeptides have been shown to cause smooth-muscle contraction and, in addition, modulate the production of pro-inflammatory molecules by leucocytes. The aim of the present review is to provide an overview of the molecular mechanisms by which neurotrophins and neuropeptides are involved in neuro-immune cross-talk in allergic asthma.

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Section: Neurotrophins and Earsupporting

confidence: 66%

The contribution of neurotrophins to the pathogenesis of allergic asthma

Rochlitzer

Nassenstein

Braun

2006

Biochemical Society Transactions

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“…On the other hand, administration of anti-NGF antibodies did not alter serum NGF concentrations or NGF content in the rostral back skin in either experiment (data not shown). Anti-NGF antibodies against 2.5 S NGF can block the effects of NGF in vitro (29) and in vivo (30). In the skin, NGF synthesized and released by keratinocytes (31 -33) plays an important role in the survival and development of the peripheral nervous system (12).…”

Section: Discussionmentioning

confidence: 99%

Effects of Anti-Nerve Growth Factor Antibody on Symptoms in the NC/Nga Mouse, an Atopic Dermatitis Model

2005

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Abstract. Nerve growth factor (NGF) is an important substance in the skin, where it can modulate nerve maintenance and repair. However, the direct link between NGF and pruritic disease such as atopic dermatitis is not yet fully understood. To determine whether NGF plays a major role in atopic dermatitis and in the development or maintenance of skin lesions, we performed a study using NC / Nga mice and compared mice with and without skin lesions. Our examinations of the NC / Nga mice sought to detect nerve fibers in the epidermis, measured serum and skin NGF content, and observed skin NGF by immunohistochemistry staining. We also examined the effects of anti-NGF antibody on dermatitis symptoms in NC / Nga mice. In these mice, nerve fibers were significantly increased in the epidermis of lesioned skin, and the NGF content of the serum and skin was significantly elevated. Anti-NGF antibodies significantly inhibited the development and proliferation of skin lesions and epidermal innervation and significantly inhibited any growth in scratching but did not ameliorate scratching already developed. Our findings suggest that NGF plays important roles in the pathogenesis of atopic dermatitis-like skin lesions and that inhibiting the physiological effects of NGF or suppressing increased NGF production may prevent or even moderate the symptoms of atopic dermatitis.

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“…The antineoplastic efficacy of this preparation was tested in immunodepressed mice grafted with representative tumoral lines previously characterized in vitro for their sensitivity to AG879 and neutralizing anti-TrKA IgG. Previously, AG879 has been administered in vivo either topically [47] or systemically but at low dosages and using DMSO as a vehicle [48]. The improved in-vivo efficacy of AG879 in liposomes showing a significant decrease of cancer mass after treatment with AG879 is consistent with the in-vitro data and its new preparation.…”

Section: Discussionmentioning

confidence: 99%

Role of nerve growth factor and its receptors in non-nervous cancer growth: efficacy of a tyrosine kinase inhibitor (AG879) and neutralizing antibodies antityrosine kinase receptor A and antinerve growth factor: an in-vitro and in-vivo study

Rende¹,

Pistilli²,

Stabile³

et al. 2006

Anti-Cancer Drugs

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Neurotrophins, originally identified as neuronal survival and differentiation factors, exert their actions through tyrosine kinase receptors such as TrKA, in the case of the nerve growth factor. Neurotrophins also interact with p75, a common receptor devoid of kinase activity and connected to apoptosis. Here we show that nerve growth factor, TrKA and p75 are expressed in cell lines of human cancers of various non-neuronal lineages, including a panel of muscular sarcomas, and we show that all cell lines investigated actively release nerve growth factor into the medium. Treatment by AG879 (a tyrosine kinase inhibitor that inhibits TrKA phosphorylation, but not TrKB and TrKC) or by neutralizing antibodies anti-nerve growth factor and anti-TrKA dramatically decreases their proliferation with a variable increase in apoptosis. Similarly, p75 transfection induced a significant increase in apoptosis. Furthermore, for the first time we have determined by high-performance liquid chromatography the pharmacokinetic profile of a novel preparation of AG879 and we have established an optimal plasmatic concentration for in-vivo administration. Treatment with AG879 in immunodepressed mice grafted with leiomyosarcoma or promyelocytic leukemia cells resulted in dramatic reductions in tumor sizes. In conclusion, our data have a novel preclinical potential for revealing a possible therapeutical utility in targeting in-vivo nerve growth factor/TrKA by AG879 or neutralizing antibody anti-TrKA in cancer proliferation and in muscle sarcomas, in particular.

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Antibodies directed against nerve growth factor inhibit the acute bronchoconstriction due to allergen challenge in guinea‐pigs

Abstract: These findings offer a new potential therapeutic strategy for the treatment of allergic asthma.

Cited by 34 publications

References 31 publications

The contribution of neurotrophins to the pathogenesis of allergic asthma

The contribution of neurotrophins to the pathogenesis of allergic asthma

Effects of Anti-Nerve Growth Factor Antibody on Symptoms in the NC/Nga Mouse, an Atopic Dermatitis Model

Role of nerve growth factor and its receptors in non-nervous cancer growth: efficacy of a tyrosine kinase inhibitor (AG879) and neutralizing antibodies antityrosine kinase receptor A and antinerve growth factor: an in-vitro and in-vivo study

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