interleukin-8 and ozagrel

This study examined the effect of ozagrel, a thromboxane A(2) synthase inhibitor, on the accumulation of leucocytes and chemokine mRNA expression in lungs experimentally injured using oleic acid (OA). OA injection into guinea pigs rapidly increased thromboxane A(2) generation and subsequently increased total protein concentration and the numbers of macrophages and neutrophils in bronchoalveolar lavage fluid and increased monocyte chemoattractant protein-1 and interleukin-8 mRNA expression in the whole lung. Administration of ozagrel prevented these changes associated with OA injection. Ozagrel is a promising drug candidate for preventing acute lung injury.

Topics: Acute Lung Injury; Animals; Bronchoalveolar Lavage Fluid; Chemokine CCL2; Eosine Yellowish-(YS); Guinea Pigs; Interleukin-8; Leukocyte Count; Macrophages; Male; Methacrylates; Methylene Blue; Neutrophils; Oleic Acid; Proteins; RNA, Messenger; Staining and Labeling; Thromboxane A2; Time Factors

To clarify whether thromboxane A2 (TXA2) is involved in type III and IV allergy, or so called "cell-mediated allergy", we studied the effect of a specific TXA2 synthetase inhibitor, sodium ozagrel (OKY-046) on peripheral blood mononuclear cells and neutrophils in adult intractable asthmatics. The results revealed, firstly, that lymphocyte blastogenesis and interleukin-2 (IL-2) production from peripheral blood mononuclear cells stimulated by PHA and Candida antigen in intractable asthmatics was significantly suppressed dose-dependently by OKY-046. Secondly, there was a tendency that neutrophil chemotactic factor (NCF) and eosinophil chemotactic factor (ECF) from peripheral blood mononuclear cells stimulated by Candida antigen in intractable asthmatics were suppressed by OKY-046. Thirdly, leukotriene (LTC4) and superoxide (O2-) production from peripheral blood neutrophils in intractable asthmatics was significantly suppressed dose-dependently by OKY-046. That is, OKY-046 has a suppressive effect on type IV allergy caused by lymphocyte activation and on mediator release from neutrophils. These results suggest that TXA2 plays an important role in the development of bronchial asthma and OKY-046 might be a useful drug in the treatment of intractable asthmatics.

Topics: Adult; Aged; Asthma; Depression, Chemical; Dose-Response Relationship, Drug; Female; Humans; Interleukin-2; Interleukin-8; Lymphocyte Activation; Lymphocytes; Male; Methacrylates; Middle Aged; Neutrophils; SRS-A; Superoxides; Thromboxane-A Synthase