The data suggest that serum ECP level reflects the intensity of eosinophilic airway inflammation, as well as the disease activity, and may be useful as an inflammatory marker in asthma.

Human alveolar macrophages (AM) can produce potent reactive oxygen intermediates (ROI) and arachidonic acid metabolites (eicosanoids), which have important roles in host defense and the pathogenesis of some diseases of the lung. Bacterial lipopolysaccharide (LPS) is believed to cause profound lung injury and can prime mouse peritoneal macrophages for the enhanced secretion of ROI and eicosanoids. Therefore, we investigated the effect of LPS pretreatment on the ability of AM to release superoxide anions (O2-) and leukotriene B4 (LTB4). LPS can prime AM for the enhanced secretion of O2- and LTB4, regardless of whether they are derived from nonsmokers or smokers. Moreover, judging from the time-response characteristics, this priming for LTB4 release could be inhibited in the later stages of pretreatment, when the O2(-)-releasing capacity was enhanced. The priming inhibition was prevented, at least in part, by cycloheximide, but not by SOD and/or catalase. In addition, cycloheximide also inhibited the priming for O2- release. Hence, protein synthesis might be necessary for the priming for O2- release and for inhibiting the priming for LTB4 release. This phenomenon of self-limiting the priming response with LPS seems to be very important when we consider the high oxygen tension in the lungs and the many bacterial substances inspired into alveoli.

The inhalation of isocyanates, such as toluene diisocyanate (TDI), diphenylmethane diisocyanate (MDI), and hexamethylene diisocyanate (HDI) can induce hypersensitivity pneumonitis (HP) as well as bronchial asthma in humans, but the precise pathological features and their pathogenetic mechanisms have not been elucidated. To provide insight into the pathological features of isocyanate-induced hypersensitivity pneumonitis in humans, we repeatedly exposed guinea-pigs to TDI following previous sensitization to TDI and examined the inflammatory response in the pulmonary lesions. Following sensitization with 10% TDI ethyl acetate solution for seven consecutive days, guinea-pigs were exposed to 5% TDI ethyl acetate solution once a week for 4 weeks. As a control, guinea-pigs were exposed to ethyl acetate alone in the same manner. Furthermore, other guinea-pigs received a single exposure to 5 or 20% TDI ethyl acetate solution. The TDI solutions or ethyl acetate were applied to the bilateral nasal mucosa of guinea-pigs for 30 s-day-1. Histological examination of lung specimens of guinea-pigs repeatedly exposed to TDI after previous sensitization by TDI inhalation revealed interstitial pneumonitis-like lesions in which mononuclear cells and eosinophils were mainly involved. Lungs of control and nonsensitized guinea-pigs showed insignificant histological changes. We demonstrated that interstitial pneumonitis-like lesions, indistinguishable from isocyanate-induced hypersensitivity pneumonitis in humans, can be caused by repeated but not single exposure to TDI in guinea-pigs.