Go Matsuzaki

Increased IL‐6 and IL‐8 in bronchoalveolar lavage fluids (BALF) from patients with sarcoidosis: correlation with the clinical parameters

A variety of cytokines have been implicated in the pathogenesis of pulmonary sarcoidosis, but the exact roles of IL‐6 and IL‐8 are not yet clear. We studied these cytokine levels in BALF from patients with pulmonary sarcoidosis, idiopathic pulmonary fibrosis (IPF), systemic screlosis (SSc) with interstitial lung disease and control subjects. IL‐6 and IL‐8 levels were significantly elevated in sarcoidosis, IPF and SSc with interstitial lung disease compared with control subjects. Subjects with sarcoidosis had significantly increased levels of both cytokines compared with controls when the cytokine values were corrected by the total albumin content and the two cytokine levels correlated with each other (r=0.876). BALF IL‐6 levels correlated with percent lymphocytes and percent CD3+ cells. Moreover, when sarcoidosis patients were divided into three groups, those who needed steroid therapy or had progressive disease showed increased cytokine levels in BALF over stable or improved patients. These observations suggest that locally derived IL‐6 and IL‐8 were increased in sarcoidosis and correlated with activity of this granulomatous lung disease.

T-Cell-Dependent Accumulation of Eosinophils in the Lung and Its Inhibition by Monoclonal Anti-Interleukin-5

The transnasal administration of an extract of the parasite Ascaris suum to C57BL/6 mice for 3 weeks produced marked eosinophilia in the bronchoalveolar lavage (BAL) fluid. The oral administration of ciclosporin significantly suppressed the pulmonary eosinophilia. Athymic C57BL/6-nu/nu mice failed to develop pulmonary eosinophilia. These data indicate that the pulmonary eosinophilia caused by this parasite extract is T-cell-dependent. Genetically mast-cell-deficient (WB x C57BL/6) F1-W/Wv (W/Wv) mice developed marked eosinophilia in the BAL, which shows that mast cells are not necessary in the formation of lung eosinophilia in this model. Monoclonal antimurine interleukin-5 injected intraperitoneally clearly inhibited the infiltration of eosinophils in the lung, suggesting that T-cell-derived interleukin-5 is essential.

Regulation of Human IgE Production by Peripheral Blood Mononuclear Cells from Atopic Patients in Mice with Severe Combined Immunodeficiency

Human peripheral blood mononuclear cells (PBMC) were transferred (i.p.) to severe combined immunodeficient (SCID) mice. PBMC from atopic donors developed both IgE and IgG synthesis, while only IgG syn

Effect of Fibronectin on the Production of Leukotriene C4 by Eosinophils

The effect of fibronectin on leukotriene C4 (LTC4) production by eosinophils was examined. Eosinophils obtained from patients with bronchial asthma were cultured for 3 h with or without fibronectin and culture supernatants were assayed for LTC4 by specific enzyme immunoassay. LTC4 was produced in a time- and dose-dependent manner in the presence of fibronectin, and maximum production of LTC4 was observed 3 h after addition of 100 micrograms/ml of fibronectin. These results suggest that eosinophils may be activated by interaction with extracellular matrix proteins, including fibronectin, and play a role in the pathogenesis of bronchial asthma.