Endotoxin up-regulates interleukin-18: Potential role for gram-negative colonization in sarcoidosis

Rationale and Objectives: Sarcoidosis is a granulomatous disease of unknown etiology characterized by a helper T-cell type 1–mediated process. Previously we demonstrated a role for interleukin-18 in sarcoidosis. Here we examine the regulation of interleukin-18 in this condition.Methods: Cytokine levels in sarcoid epithelial lining fluid were measured by ELISA. We examined interleukin-18 promoter activity and mRNA and protein levels in the epithelial lining fluid of individuals with active sarcoidosis, and of individuals recovered from sarcoidosis, in response to purified protein derivative of Mycobacterium tuberculosis, beryllium sulfate, zirconium sulfate, aluminum sulfate, and lipopolysaccharide. Endotoxin levels in the epithelial lining fluid of individuals with sarcoidosis, individuals recovered from sarcoidosis, and control subjects were assessed by Limulus amebocyte lysate analysis. Allele-specific polymerase chain reaction was used to genotype 94 patients with sarcoidosis and 97 control subjects fo...