[Steroid resistance and lung-tissue cytokines in experimental bleomycin-induced lung fibrosis].
To examine the mechanism of steroid resistance in lung fibrosis, cytokines expressed in the lung tissue of mice with bleomycin-induced lung fibrosis were studied. 1. Glucocorticoid administration (1 mg/kg/day) did not affect the grade of lung fibrosis induced by intratracheal injection of bleomycin (3.76 micrograms/g). 2. Cytokines expressed in the lung tissue were studied with the reverse-transcriptase polymerase chain reaction. Levels of promotor cytokines, such as TNF alpha, TGF beta, INF gamma, and IL-2, were significantly higher in lung tissue from the bleomycin group. The expression of these cytokines in the glucocorticoid group was low, especially the peak value. Expression of IL-4 was high in the bleomycin group, and was not inhibited in the glucocorticoid group. Expression of the down-regulator cytokine IL-10 was also high in the bleomycin group and very low in the glucocorticoid group. 3. The non-selectivity of glucocorticoids with respect to promotor and suppressive cytokines may account in part for steroid resistance in bleomycin-induced pulmonary fibrosis.
Hosoya
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First Department of Internal Medicine, Kyorin University, School of Medicine, Tokyo, Japan.
D000818:Animals; D001761:Bleomycin; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004351:Drug Resistance; D005938:Glucocorticoids / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D005938:Glucocorticoids; D007378:Interleukins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; D007371:Interferon-gamma