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.