The clinical significance of interleukin 18 assessment in sarcoidosis patients

Introduction: Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of immune granulomas in involved organs. The cytokine profile in inflamed lesions of sarcoidosis is mainly determined by T helper 1 (Th1) cells. Interleukin 18 (IL-18) is primarily a monocyte / macrophage-derived cytokine. IL-18 has been recently identified as an IFN gamma-inducing factor. The cytokine plays an important role in the induction of Th1 response and it may be responsible for sarcoiclosis progression. The aim of the study was to assess the usefulness of IL-18 estimation in the sarcoidosis diagnosis and the disease course prognosis. Material and methods: The diagnosis of sarcoidosis was established in 88 patients (the mean age of 38.1 +/- 10.8 years). We measured IL-18 level in plasma and bronchoalveolar lavage fluid (BALF) cell culture supernatant (CCS) using the enzyme-linked immunoassay technique (ELISA). We also performed the flow cytometric analysis of BALF lymphocyte phenotype. Statistica 5.0 and non-parametric tests: the Mann-Whitney U-test and the Spearman correlation test, were used for statistical analysis. Results: The patient group consisted of 55 subjects without acute symptoms of sarcoidosis, 14 patients with acute Lofgren syndrome and 19 subjects with Lofgren syndrome in the past. Lung hilar lymphadenopathy was diagnosed in 49 patients and lung interstitial changes in 39 subjects. After 6-month-observation, 49 patients were in remission, 20 subjects manifested persistent disease and 19 patients had sarcoiclosis progression. Plasma IL-18 Level was significantly (P < 0.0001) higher in sarcoidosis patients (383 +/- 250 pg/ml) than in control subjects (146 +/- 72 pg/ml). Plasma IL-18 Level was similar both in subjects with Lofgren syndrome and in other patients. However, IL-18 level in BALF CCS was significantly (P < 0.05) lower in Lofgren syndrome patients than in subjects without acute manifestation of the disease. The highest IL-18 level in plasma was found in patients with disease progression, in subjects with lung interstitial changes and in patients with extrapulmonary manifestation of the disease. We observed a positive correlation between plasma IL-18 Level and the percentage of BALF lymphocytes (R = 0. 202, P = 0. 06) as well as the percentage of activated HLA DR+T cells (R = 0.23, P < 0.05). There was a negative correlation between the IL-18 Level in BALF CCS and the percentage of BALF CD3-positive and CD4-positive lymphocytes (R = -0.27, -0.23, P < 0.05). Conclusion: IL-18 may play a significant rote in the prolongation of sarcoidosis course. Its estimation may become a good prognostic factor, which should be analyzed together with other factors useful in sarcoidosis monitoring. (c) 2006 Elsevier Ltd. All rights reserved.