Expression and Regulation of Inflammatory Cytokine Genes In Vitro and In Vivo

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We investigated the in vitro and in vivo role of inflammatory cytokines, IL-8 and MCAF with neutrophil and monocyte chemotactic activities, which is induced rapidly by the stimulation of IL-1 or TNF.Our results indicate that(1) Induction of IL-8 and MCAF Genes in Various Tumor Cell Lines and Its Regulation by Glucocorticoid : Fibrosarcoma and glioblastoma cell lines were found to express high levels of these inflammatory cytokines genes. The regulatory elements in IL-8 gene and nuclear factors (NF-kB, C/EBP, AP-1) were identified, particularly in interests of glucocorticoid action (Mukaida et al. Immunol.1992 ; Eur.Cytok, Netw 1993 ; J.Biol.Chem.1994 in press).(2) Determination of Inflammatory Cytokines In Various Disease States : Production of IL-8 and MCAF in various infectious and inflammatory diseases were determined using ELISA methods. Significant levels of IL-8 was observed in urines from urinary tract infection and amniotic fluids from pregnant women. Similarly, significant levels of IL-8 were detected in synovial fluids from rheumatoid arthritis or pleural fluids from cancer patients, providing valuable monitoring in these inflammatory responses.(Saito et al. Cytokine 1993 ; Ko et al. Infect. Immunity 1993 ; Tsuchiya et al.Cytokine 1993)(3) Large-scale Production of MCAF and In Vivo Application : Administration of MCAF was found to be effective to protect mice from lethal Salmonella and Pseudomonas infection in vivo (Nakano et al.Infect.Immun.1994)