Mediators of Inflammation in the Early and the Late Phase of Allergic Rhinitis

Inga Hansen; Ludger Klimek; Ralph Mösges; Karl Hörmann

Disclosures

Curr Opin Allergy Clin Immunol. 2004;4(3) 

In This Article

Nerve Growth Factor: NGF Augments the Allergic Reaction

Päth et al.[24*] investigated the influence of nerve growth factor (NGF) on allergic early-phase reaction. Substance P is known to trigger smooth muscle constriction and acute inflammation,[25,26] whereas NGF enhances the production of substance P by neurons.[27,28,29,30] Neurotropins such as NGF seem to act as mediators in the interactions between immune and nerve cells.[31] NGF is produced not only by neurons and nerve-associated cells, but also by immune cells such as mast cells, macrophages, T cells and B cells. Local NGF upregulation has been found in allergic airway inflammation, and NGF was identified as an amplifier of the Th2 immune response and shown to contribute to the development of airway hyperreactivity.[32]

Päth et al.[24*] investigated the role of NGF in experiments with transgenic mice encoding NGF and wild type mice. Mice were sensitized to ovalbumin. During allergen challenge of ovalbumin, both control mice and anti-NGF-treated mice responded immediately with a marked fall in expiratory flow-50 values (measured with head-out body plethysmography; P<0.001). Interestingly, the airflow limitation lasted at least 25 min in control mice, whereas the anti-NGF treated group recovered within 15 min. Transgenic mice (NGF) showed a significantly higher degree of expiratory airflow limitation than wild type mice. In the anti-NGF-treated mice, the amount of eosinophil airway recruitment was significantly reduced (P<0.001), whereas numbers of macrophages, lymphocytes, and neutrophils were not altered. Local production of IL-4 and IL-5 was significantly reduced (P<0.001), whilst IFN-γ was not affected. The group of NGF-transgenic mice displayed a significantly higher influx of eosinophils, lymphocytes, and neutrophils. Lymphocyte recruitment was seen as a result of ovalbumin aerosol challenges. The measurement of total and ovalbumin-specific IgE antibody levels revealed no significant differences between the different groups of mice. The development of methacholine-induced airway hyperreactivity was not affected by treatment with anti-NGF or NGF. NGF-transgenic mice showed a significantly higher increase in serotonin after intranasal allergen challenge than wild type animals (P<0.05). No differences in sensory reactivity were found.

These interesting results demonstrate that NGF augments the allergic early-phase reaction via increased release of mast cell mediators. Furthermore, it seems to be a promoter of allergic airway inflammation, seen as an increase in eosinophil and lymphocyte recruitment as well as a rise in local IL-4 and IL-5 production after allergen challenge. Overexpression of NGF enhances sensory hyperresponsiveness, but neither anti-NGF nor NGF treatment alters unspecific airway hyperreactivity. NGF may participate in the enhancement of IgE levels, as it induces differentiation of activated B cells into plasma cells.[33,34,35] NGF appears as a mediator between the immune and the nervous system.

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