Rates of infiltration by macrophages and dendritic cells and expression of interleukin-18 and interleukin-12 in the chronic inflammatory lesions of Sjögren's syndrome: correlation with certain features of immune hyperactivity and factors associated with high risk of lymphoma development.

OBJECTIVE: To evaluate the expression profile of infiltrating macrophages and dendritic cells (DCs) as well as of interleukin-18 (IL-18) and IL-12 in the minor salivary gland (MSG) lesions of patients with Sjögren's syndrome (SS), and to assess the relationship of these factors with disease parameters. METHODS: Macrophages, DCs, T cells, B cells, proIL-18, mature IL-18, and IL-12 were detected by single- and double-labeling immunohistochemistry in MSG specimens from 21 patients with primary SS (13 of 21 tested for IL-12), 7 patients with secondary SS, and 9 disease control patients. Expression profiles were assessed for correlations with various disease parameters, including adverse predictors of lymphoma development. RESULTS: MSGs from patients with SS (but not from disease controls) manifested increased infiltration by macrophages and DCs, strong expression of IL-18 by macrophages (particularly in B cell-rich areas and in germinal center-like structures in primary SS), and expression of IL-12 by mononuclear cell infiltrates. In primary SS, high infiltration by macrophages correlated with SG enlargement (P = 0.01). The DC infiltration rate correlated positively with the macrophage infiltration rate (P = 0.04), occurrence of SG enlargement (P = 0.03), and presence of C4 hypocomplementemia (P = 0.05), and inversely with serum C4 complement levels (P = 0.001). The rate of infiltration by IL-18-expressing cells correlated positively with biopsy focus scores (P < 0.001), larger infiltrates of macrophages (P = 0.01), DCs (P = 0.01), and B cells (P = 0.02), and SG enlargement (P = 0.02), and negatively with serum C4 complement levels (P = 0.02). The rate of infiltration by IL-12-expressing cells correlated inversely with that by IL-18-expressing cells (P = 0.001), biopsy focus scores (P = 0.003), and SG enlargement (P = 0.01), and positively with serum C4 complement levels (P = 0.05). CONCLUSION: In patients with primary SS, infiltration of the SG by macrophages and DCs and expression of IL-18 and IL-12 appear to play active roles in the expansion and organization of infiltrative injuries and have a correlation with certain predictors of lymphoma development.