Elevated expression of interleukin-18 in the granulomatous lesions of muscular sarcoidosis.
In an attempt to understand the role of interleukin-18 (IL-18) in the pathogenesis of sarcoidosis, we examined the expression of IL-18 in normal muscle and in muscle biopsies from six patients with muscular sarcoidosis. Western blot analysis demonstrated that IL-18 was identified only in homogenates of granulomatous muscle tissues, but not in normal muscle tissue homogenates. By immunohistochemistry, strongly IL-18-positive cells were distributed predominantly at the boundary zone of the granulomas. They were recognized as activated macrophages by double staining with anti-CD68. Epithelioid cells showed only faint reactivity. Serum IL-18 levels of patients with sarcoidosis were significantly increased compared to those of healthy volunteers. Unlike protein expression, IL-18 mRNA expression was detected even in normal muscles. Our results coupled with those of previous investigations demonstrating activity of IL-18 in inducing interferon-gamma production suggest a significant role of IL-18 in the pathogenesis of sarcoidosis.
Fukami
T
T
Third Department of Internal Medicine, Oita Medical University, 1-1 Idaigaoka, Oita, 879-5593, Japan. fukami@oita-med.ac.jp
Miyazaki
E
E
Matsumoto
T
T
Kumamoto
T
T
Tsuda
T
T
D000328:Adult; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006099:Granuloma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D009135:Muscular Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D012507:Sarcoidosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic; D015854:Up-Regulation
D016207:Cytokines; D020382:Interleukin-18; D012333:RNA, Messenger