The clinical significance of interleukin 18 assessment in sarcoidosis patients.
BACKGROUND
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 IFNgamma-inducing factor. The cytokine plays an important role in the induction of Th1 response and it may be responsible for sarcoidosis progression. The aim of the study was to assess the usefulness of IL-18 estimation in the sarcoidosis diagnosis and the disease course prognosis.


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 Löfgren syndrome and 19 subjects with Löfgren 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 sarcoidosis progression. Plasma IL-18 level was significantly (P<0.0001) higher in sarcoidosis patients (383+/-250pg/ml) than in control subjects (146+/-72pg/ml). Plasma IL-18 level was similar both in subjects with Löfgren syndrome and in other patients. However, IL-18 level in BALF CCS was significantly (P<0.05) lower in Löfgren 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).


CONCLUSIONS
IL-18 may play a significant role 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.
Kieszko
Robert
R
Department of Pneumology, Oncology and Allergology, Medical University of Lublin, Lublin, Poland. pulm.dept@am.lublin.pl
Krawczyk
Paweł
P
Jankowska
Olga
O
Chocholska
Sylwia
S
Król
Anna
A
Milanowski
Janusz
J
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002478:Cells, Cultured; D018450:Disease Progression; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000032:analysis* / Q000097:blood; D018655:Lymphocyte Count; D008297:Male; D012129:Respiratory Function Tests; D012507:Sarcoidosis / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology
D015415:Biomarkers; D020382:Interleukin-18