ROLE OF NERVE GROWTH-FACTOR IN A MOUSE MODEL OF ALLERGIC AIRWAY INFLAMMATION AND ASTHMA

The role of nerve growth factor (NGF), a potent mediator acting in the development and differentitation of both neuronal and immune cells, w as examined in a mouse model of allergic asthma. NGF-positive cells we re detected in the inflammatory infiltrate of the lung and enhanced le vels of NGF were detected in serum and broncho-alveolar lavage fluids. Mononuclear cells in inflamed airway mucosa as well as broncho-alveol ar macrophages were identified as one source of NGF production. Spleni c mononuclear cells from allergen-sensitized mice produced NGF in resp onse to allergen. They responded to exogenously added NGF with a dose- dependent increase in IL-4 and IL-5 production and augmented IgE and I gG(1) synthesis. In contrast, IFN-gamma and IgG(2a) levels remained un affected. The effects were NGF specific, since they could be blocked b y an anti-NGF-antibody. Nasal application of anti-NGF to allergen-sens itized mice significantly reduced IL-4 and prevented development of ai rway hyperreactivity. These results show that allergic airway inflamma tion is accompanied by enhanced local NGF production that acts as an a mplifier for Th2 effector functions and plays an important role in the development of airway hyperreactivity. Therefore it is suggested that NGF may serve as a link between the immune and nerve system.