Elevated expression of IL-18 in Sjögren's syndrome: distinct expression patterns of the active and proactive forms

Background

IL-18 is an important immunoregulatory and proinflammatory cytokine that is produced by various cell types, including antigen-presenting cells and epithelial cells. IL-18 is synthesized as a biologically inactive precursor molecule (proactive IL-18) that converts into an active, mature molecule after enzymatic cleavage. Upregulated levels of IL-18 have been identified in several autoimmune diseases, but its role in Sjögren's syndrome (SS) is uncertain.

Objective

The aim of the study was to investigate the role of IL-18 in SS.

Methods

RT-PCR analysis, immunohistochemistry and immunoblotting (with distinct anti-IL-18 antibodies against the proactive and active forms) were applied for the detection of IL-18 in cultured SG epithelial cell (SGEC) lines established from patients with SS (n = 5) and from non-SS disease control patients (n = 5), as well as in minor SG biopsy specimens obtained from patients with primary SS (n = 12), secondary SS (n = 5) and non-SS disease controls (n = 7) were used.

Results

The expression of IL-18 mRNA was detected in all SGEC lines tested. In addition, cultured SGEC express constitutively the proactive, but not the mature, form of IL-18 protein, as demonstrated by immunoblotting. In minor SG biopsies, strong expression of the IL-18 proactive protein was detected in the ductal epithelial and CD68⁺ infiltrating macrophages of the SS patients, but not in the controls. The expression of the active form of IL-18 was detected only in SS patients and mainly in those with extended inflammatory lesions. In these samples, active IL-18-positive cells were observed exclusively among the CD68⁺ macrophages of the mononuclear cell infiltrates.

Conclusion

Our data possibly indicate the role of IL-18 in the expansion of lymphoepithelial lesions of SS patients. SGEC were found to express only the proactive form of IL-18, the biological significance of which remains to be determined.