Interleukin 1 slowly increases lung fibroblast Cu-Zn superoxide dismutase activity levels

Certain pulmonary stress raises rat lung Cu-Zn superoxide dismutase (SOD) activity levels, but cytokines released during stress are reported to exert no regulatory effects on Cu-Zn SOD levels in cultured cells. In contrast, our study found that interleukin 1 (IL-1) can increase Cu-Zn SOD activities in human W138 lung fibroblasts. The difference in results could be explained by differences in experimental conditions. The increases seen here did not occur during the first 24 hr, but Cu-Zn SOD activities more than doubled by 3 days. In addition, little increase occurred unless the medium was changed at 24-hr intervals. On the other hand, some other potential experimental variables showed little or no effects on IL-1-induced increases in Cu-Zn SOD activities. These variables included IL-1 isoform (alpha, beta, or both), IL-1 concentration (0.5, 2, 5, or 7 units IL-1 alpha/ml medium), and the presence or absence of exogenously added copper as CuO or ceruloplasmin. In addition, combining IL-1 with dexamethasone, a synthetic glucocorticoid that enhances some IL-1 actions, produced only additive, not synergistic, increases in Cu-Zn SOD activities. In conclusion, IL-1, in several different experimental protocols, raised lung fibroblast Cu-Zn SOD activity levels, but only after a 1 day lag time. Stress-induced increases in Cu-Zn SOD activity levels in vivo also tend to occur only after lag times.