1988 年 108 巻 4 号 p. 251-270
Chemical mediators of inflammation, responsible for vascular permeability increasing activity, were analyzed in inflammation models of air pouch type in rats. By use of carrageenin-induced air pouch model, prostaglandin (PG) E2 was found to be an important chemical mediator for vascular permeability response in the acute exudative stage but not in the chronic proliferative stage of inflammation. Vascular permeability response at the chronic proliferative stage was suppressed by the steroidal anti-inflammatory drugs but not by cyclooxygenase inhibitors, suggesting that the steroidal anti-inflammatory drugs are more potent than the cyclooxygenase inhibitors. To get further insight into the mechanism of allergic inflammation, an allergic inflammation model of air pouch type in rats was established by using azobenzene arsonate-conjugated acetyl bovine serum albumin as an antigen. The anaphylactic increase in vascular permeability was found to be substantially mediated by histamine and serotonin although the contents of slow reacting substance (SRS), lyso-form of platelet activating factor (PAF) were high in the pouch fluid in this phase. The possibility of participation of SRS, PG and PAF was found to be remote. β-Agonists were found to suppress the anaphylactic increase of vascular permeability without inhibiting mast cell degranulation. They exert their effects by inhibiting the reactivity of local vasculature to chemical mediators released from mast cells. A model for recurrent allergic inflammation was developed in order to clarify chemical mediators in chronic diseases such as rheumatoid arthritis. Five days after the 1st antigenic challenge, the antigen solution was again injected into a granulation tissue capsule holding around 10 ml of exudate. The role of PGE2 in vascular permeability responses in both types of allergic inflammation was examined to show that there exists a certain phase where PGE2 has no significant role in vascular permeability responses. Characterization of chemical mediators in that phase remains to be elucidated. Tumor promoters in two-stage carcinogenesis model in mouse skin, whether 12-O-tetradecanoylphorbol 13-acetate (TPA) type or non-TPA type, were found to have a very potent stimulating activity on arachidonic acid metabolism in rat peritoneal macrophages. Chemical mediators responsible for the tumor promoter-induced inflammation were identified as histamine, serotonin and PGE2. The role of the inflammatory reactions inducible by these promoters for the tumor promotion process also remains to be elucidated.