Article

The clinical significance of interleukin 18 assessment in sarcoidosis patients.

Department of Pneumology, Oncology and Allergology, Medical University of Lublin, Lublin, Poland.
Respiratory Medicine (impact factor: 2.47). 04/2007; 101(4):722-8. DOI:10.1016/j.rmed.2006.08.019
Source: PubMed

ABSTRACT 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.
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.
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).
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.

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Keywords

19 subjects
 
20 subjects manifested persistent disease
 
55 subjects
 
acute Löfgren syndrome
 
BALF lymphocytes
 
CD4-positive lymphocytes
 
control subjects
 
disease course prognosis
 
highest IL-18 level
 
IL-18 level
 
lung interstitial changes
 
multisystemic disease
 
negative correlation
 
patient group
 
Plasma IL-18 level
 
positive correlation
 
Spearman correlation test
 
T helper 1
 
Th1 response
 
unknown etiology
 

Robert Kieszko