Anti-inflammation. Methodology and a means for the suppression of inflammation. From an aspect of arachidonic acid cascade.:<I>From an aspect of arachidonic acid cascade</I>
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概要
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Using an air pouch type allergic inflammation model in rats, roles of arachidonate metabolites in inflammatory responses were investigated in order to define characteristics of allergic inflammation in rats, and to get further insight into a methodology for suppression of inflammation from a veiw point of arachidonic acid metabolism. Biochemical and pharmacological analysis revealed following results; (1) Peptide-leukotrienes do not play any significant role in vascular permeability increase in anaphylaxis phase. (2) Leukotriene B<SUB>4</SUB> also plays no role in neutrophil infiltration, suggesting that participation of lipoxygenase products in inflammatory responses is negligible in rats. (3) In contrast, antagonists of platelet activating factor (PAF) efficiently suppressed neutrophil infiltration into the inflammatory locus indicating that PAF plays a significant role for neutrophil infiltration. (4) Prostaglandin E<SUB>2</SUB> participates in vascular permeability increase at a definite period, and in stimulation of neutrophil infiltraltion by suppressing histamine production at the inflammatory locus. (5) Cyclooxygenase inhibitors suppress vascular permeability and neutrophil infiltration. Suppression of neutrophil infiltration by cyclooxygenase inhibitors is mediated by stimulation of histamine production through inhibition of prostaglandin E<SUB>2</SUB> biosynthesis. Histamine suppresses neutrophil infiltration by acting on histamine H<SUB>2</SUB> receptors of neutrophils.<BR>Finally, present situation and point at issue for suppression of inflammation through regulation of arachidonic acid metabolism is discussed.
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