Interleukin-18 expression in BAL cells of sarcoidosis patients is decreased in vivo but protein secretion is not impaired in vitro.
Recently, increased expression of interleukin-18 (IL-18) has been shown in sarcoid airway epithelium. However, IL-18 expression has not been investigated extensively in bronchoalveolar lavage (BAL) cells in sarcoidosis yet. Expression of IL-18 and tumour necrosis factor-alpha (TNFalpha) mRNA in cells of the BAL of 23 patients with sarcoidosis and nine healthy volunteers was determined using semiquantitative RT-PCR. IL-18 protein in BAL cells was investigated by immunocytochemistry (ICC). IL-18 protein levels in BAL cell culture supernatants from patients and controls with and without LPS stimulation were measured by enzyme-linked immuno-sorbent assay. BAL cells from patients were stimulated with either IL-10 or IL-13 and IL-18 protein levels were determined. IL-18 mRNA expression was significantly decreased in BAL cells of patients compared to control subjects (1.62 +/- 0.27 vs. 4.29 +/- 0.77, P < 0.05). TNFalpha mRNA expression was significantly increased in BAL cells of patients in comparison to control subjects (0.63 +/- 0.09 vs. 0.11 +/- 0.08, P < 0.05). ICC showed less positive alveolar macrophages in sarcoidosis patients than in control subjects (26 vs. 53%). IL-18 protein levels did not differ significantly between both groups. Stimulation with IL-10 significantly reduced IL-18 protein concentration in sarcoidosis patients. Our results suggest that BAL cells may not be the main source of IL-18 production in sarcoidosis in vivo. Since IL-18 production of BAL cells was not impaired in culture antiinflammatory cytokines might contribute to decreased IL-18 expression in vivo.
Department of Internal Medicine, University Hospital Eppendorf, Hamburg, Germany. hans-peter.hauber@mcgill.ca
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D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017565:Sarcoidosis, Pulmonary / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D018793:Interleukin-13; D020382:Interleukin-18; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10