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This Article Full Text Full Text (PDF) All Versions of this Article: 289/2/L280    most recent 00380.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Nakatani-Okuda, A. Articles by Okamura, H. Search for Related Content PubMed PubMed Citation Articles by Nakatani-Okuda, A. Articles by Okamura, H.

Protection against bleomycin-induced lung injury by IL-18 in mice

¹Pediatrics, ²Institute for Advanced Medical Sciences, ³Surgical Pathology, ⁴Department of Medical Physicochemistry and ⁵Gynecology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan

Submitted 12 October 2004 ; accepted in final form 21 March 2005

The role of interleukin (IL)-18 in the protection from interstitial pneumonia and pulmonary fibrosis induced by bleomycin (BLM) was investigated by comparing the severity of BLM-induced lung injuries between wild-type and C57BL/6 mice with a targeted knockout mutation of the IL-18 gene (IL-18–/– mice). IL-18–/– mice showed much worse lung injuries than wild-type mice, as assessed by the survival rate, histological images, and leukocyte infiltration in the bronchoalveolar lavage fluid and myeloperoxidase activity. In wild-type mice, administration of IL-18 before BLM instillation resulted in suppression of lung injuries, increases in the hydroxyproline content, and decreases in the granulocyte-macrophage colony-stimulating factor content in the lung. Preadministration of IL-18 also resulted in prevention of the reduction of the lung IL-10 content caused by BLM-induced damage of alveolar epithelial. BLM instillation suppressed superoxide dismutase (SOD) activity in IL-18–/– mice to a greater extent than in wild-type mice. Pretreatment of IL-18 augmented Mn-containing superoxide dismutase (Mn-SOD) messenger RNA expression and SOD activity in the lung and prevented the reduction of SOD activity caused by BLM in both wild-type and IL-18–/– mice. These results suggest that IL-18 plays a protective role against BLM-induced lung injuries by upregulating a defensive molecule, Mn-SOD.

Mn-superoxide dismutase; superoxide; interleukin-18

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