Theophylline attenuates the neutrophil-dependent augmentation of eosinophil trans-basement membrane migration.

BACKGROUND: Recent evidence suggests that both neutrophilic and eosinophilic inflammation persist in the airways of patients with severe asthma. Neutrophils can secrete a variety of mediators which may augment the migration of eosinophils. We have reported that activated neutrophils augment the trans-basement membrane migration (TBM) of eosinophils in vitro. Theophylline has been shown to modulate some functions of both neutrophils and eosinophils. The objective of this study was to evaluate whether theophylline modulates the neutrophil-dependent augmentation of eosinophil TBM. METHODS: Eosinophils and neutrophils were isolated from peripheral blood collected from healthy donors and were then preincubated with either 0.1 mM theophylline or the medium control. The TBM of eosinophils in response to IL-8 was evaluated in the presence or absence of neutrophils by using the chambers with a Matrigel-coated Transwell insert. The generation of O(2)(-) was evaluated by the cytochrome c reduction assay. RESULTS: As previously reported, IL-8-stimulated neutrophils significantly augmented the TBM of eosinophils. Theophylline significantly attenuated the neutrophil-dependent augmentation of eosinophil TBM (p < 0.001) and did not directly modify the TBM of neutrophils in response to IL-8 or LTB4. Similarly, the LTB4-induced TBM of eosinophils was not modified by theophylline. Finally, theophylline attenuated the superoxide anion generation from IL-8-stimulated neutrophils on the Matrigel-coated plates. CONCLUSIONS: Our results show that theophylline can attenuate the neutrophil-dependent augmentation of eosinophil TBM. This effect is possibly attributable to the suppression of neutrophil activation provoked by the combination of basement membrane and IL-8.

[Ct findings of drug-induced pneumonitis--characteristic CT findings by histological group and subgroup].

We examined the chest CT results of 27 cases of drug-induced pneumonitis. We classified the subjects into 3 groups in accordance with the clinicopathological findings: eosinophilic pneumonia (EP) group (5 cases), diffuse alveolar damage (DAD) group (3 cases), and interstitial pneumonia (IP) group (19 cases). We evaluated the CT findings in each group, and made a further subclassification. In the EP group, the CT findings were subdivided into two, namely, type A, with diffuse distribution consistent with CT findings of acute eosinophilic pneumonia; and type B, with subpleural distribution consistent with chronic eosinophilic pneumonia. In the DAD group, the CT findings were diffuse distribution of mixed ground-glass attenuation and air-space consolidation, with or without traction bronchiectasis, and without shrinking of the lung. In the IP group, the CT findings were subdivided into 3, namely type A, with ground-glass attenuation dominant, without traction bronchiectasis or shrinking of the lung, consistent with the CT findings of IP without fibrosis; type B, with air-space consolidation dominant, with traction bronchiectasis and shrinking of the lung, consistent with the CT findings of IP with fibrosis; and type C with multiple nodules dominant. Radiological differentiation of the DAD group from IP-type B may be possible by the presence or absence of a shrinking lung pattern. We concluded that the subgroups of CT findings in drug-induced pneumonitis may be useful for diagnosis of this disease, and for prognosis.

[A case of pneumonitis induced by Bofu-tsusho-san].

We encountered a patient in whom Bofu-tsusho-san (Chinese herbal drug) had induced pneumonitis. A 65-year-old man was admitted to our hospital because of cough, fever, and dyspnea about one month after treatment with Bofu-tsusho-san. BALF showed an increase in the total cell number and the percentage of lymphocytes. TBLB revealed interstitial pneumonia. The patient recovered after discontinuation of Bofu-tsusho-san alone. We diagnosed Bofu-tsusho-san-induced pneumonitis. Clinicians should be aware of drug-induced pneumonitis in patients receiving herbal drugs.