ABSTRACT
BACKGROUND AND OBJECTIVE: Acute eosinophilic pneumonia (AEP) is characterized by a massive pulmonary infiltration of eosinophils. Mechanisms regulating the selective accumulation of eosinophils in AEP have not been fully established. The objective of this study was to evaluate the mechanisms of eosinophil accumulation in alveolar spaces through examination of bronchoalveolar lavage fluid (BALF) from AEP patients (AEP-BALF). METHODS: Eosinophils were isolated from the blood of healthy subjects and were placed on a human pulmonary microvascular endothelial cell monolayer cultured on Transwell filters (Coster, Cambridge, MA, USA). A saline control solution or BALF from patients with AEP, sarcoidosis or hypersensitivity pneumonitis was applied to the lower compartment, and the transendothelial migration of the eosinophils was evaluated. The concentrations of cytokines and chemokines in BALF were also measured. RESULTS: Transmigration of eosinophils across endothelial cells was only induced by the AEP-BALF. This transmigration was blocked by anti-ß2 integrin mAb. The concentrations of eotaxin-2 and monocyte chemotactic protein (MCP)-4, which are CC chemokine receptor (CCR) 3 ligands, were elevated in the AEP-BALF, and anti-CCR3 mAb or anti-MCP-4 mAb inhibited the AEP-BALF-induced transmigration of eosinophils. Furthermore, the concentration of leukotriene (LT) B4 was increased in the AEP-BALF, and an LTB4 receptor antagonist partially suppressed the AEP-BALF-induced transmigration of eosinophils. CONCLUSION: These findings suggest that CCR3 ligands including eotaxin-2 and MCP-4, and LTB4 play a role in the accumulation of eosinophils in AEP.
Subject(s)
Cytokines/immunology , Eosinophils/immunology , Pulmonary Eosinophilia/immunology , Transendothelial and Transepithelial Migration/immunology , Adolescent , Adult , Aged , Alveolitis, Extrinsic Allergic/immunology , Bronchoalveolar Lavage Fluid , Case-Control Studies , Chemokine CCL24/immunology , Chemokines/immunology , Female , Humans , Leukocyte Count , Male , Middle Aged , Monocyte Chemoattractant Proteins/immunology , Receptors, CCR3/immunology , Sarcoidosis, Pulmonary/immunology , Young AdultABSTRACT
OBJECTIVE: The purpose of this clinical trial was to assess the efficacy of goshuyuto, a typical Kampo formula, in preventing episodes of headache in chronic headache patients. RESEARCH DESIGN AND METHODS: Because the treatment target of a Kampo formula is decided on a basis different to that of Western medicine, we first selected patients belonging to a subgroup that responded to goshuyuto before conducting the usual randomized controlled trial. During stage 1, the subjects were instructed to orally consume goshuyuto for 4 weeks. Only those subjects judged as responders advanced to stage 2, during which a double-blind, randomized, placebo-controlled study was conducted. The subjects consumed the same dose of goshuyuto or placebo for 12 weeks. RESULTS: Of the 91 subjects enrolled in stage 1, 60 were judged as responders. Of these, 53 advanced to stage 2; 28 were assigned to the goshuyuto group and 25 to the placebo group. The decrease in the number of days on which headache episodes occurred was greater in the goshuyuto group than in the placebo group (2.6 +/- 3.7 vs. 0.3 +/- 4.0 days, p = 0.034); no difference was observed with regard to the reduction in the frequency of consuming reliever medications (2.2 +/- 4.0 vs. 1.4 +/- 8.2, p = 0.672). Improvement in the associated symptoms was observed in more than 50% of the subjects in the goshuyuto group. CONCLUSION: Goshuyuto is useful in preventing episodes of headache in chronic headache patients. Responder-limited design is a candidate for evaluating Kampo medicine.
