In Vivo Suppression of NF - k B and Preservation of I k B a by Interleukin - 10 and Interleukin - 13

IL-10 and IL-13 have powerful antiinflammatory activities in vitro and in vivo. In the IgG immune complex model of lung injury in rats, exogenously administered IL-10 or IL-13 have recently been shown to suppress neutrophil recruitment and ensuing lung injury by greatly depressing pulmonary production of TNF a . Transcriptional control of the TNF a gene is regulated by the nuclear factor kappa B (NFk B). Activation of NFk B involves the degradation of its cytoplasmic inhibitor I k B a , allowing the nuclear translocation of NFk B, with ensuing transcriptional activation. In this study, we sought to determine whether the protective effects of IL-10 and IL-13 in IgG immune complex–induced lung injury were mediated by inhibition of NFk B activation. Electrophoretic mobility shift analysis of nuclear extracts from alveolar macrophages and whole lung tissues demonstrated that both IL-10 and IL-13 suppressed nuclear localization of NFk B after in vivo deposition of IgG immune complexes. Western blot analysis indicated that these effects were due to preserved protein expression of I k B a in both alveolar macrophages and whole lungs. Northern blot analysis of lung mRNA showed that, in the presence of IgG immune complexes, IL-10 and IL-13 augmented I k B a mRNA expression. These findings suggest that in vivo, IL-10 and IL-13 may operate by suppressing NFk B activation through preservation of I k B a . ( J. Clin. Invest. 1997. 100:2443–2448.)