Increased Levels of Interleukin-18 in Patients with Pulmonary Sarcoidosis

Abstract

Interleukin-18 (IL-18) has recently been identified as an interferon-gamma (IFN-gamma)-inducing factor, and it plays an important role in T helper 1 (Th1) response. We measured the serum levels of IL-18 and IFN- gamma in 37 patients with pulmonary sarcoidosis and 25 healthy control subjects. We also measured the levels of IL-18 and IFN-gamma in 10-fold concentrated bronchoalveolar lavage (BAL) fluids of 19 patients with pulmonary sarcoidosis and 9 healthy control subjects (all lifelong nonsmokers). The levels of serum IL-18 and IFN-gamma were significantly increased in patients with sarcoidosis. The levels of BAL fluid IL-18 were significantly elevated in patients with sarcoidosis, however, the IFN-gamma levels of the patients and control subjects were all below sensitivity. Serum IL-18 levels significantly correlated with serum IFN-gamma levels and lysozyme activity. The patients positive for gallium-67 ((67)Ga) scan had significantly elevated serum IL-18 levels as compared with those of the negative patients. BAL fluid IL-18 levels significantly correlated with serum IL-18 levels in patients with sarcoidosis, and there was a significant correlation between IL-18 levels and lymphocyte proportions in sarcoid BAL fluids. In patients with sarcoidosis, IL-18 seems to induce IFN-gamma production and IL-18 levels in sera may reflect disease activity of sarcoidosis.

Enhanced Expression of Type 1 Helper T-Cell Cytokines in the Myocardium of Active Cardiac Sarcoidosis

“…3,9 Preferential expression of Th1 cytokines has been reported in bronchoalveolar lavage cells and fluids from patients with pulmonary sarcoidosis. [9][10][11] In the present study, we have demonstrated for the first time enhanced expression of Th1 cytokine mRNAs in the myocardium of patients with active cardiac sarcoidosis. It is not easy to confirm the diagnosis of cardiac sarcoidosis, particularly when there is not definite extra-cardiac involvement.…”

Interleukin-18

“…In general, it appears that IL-18 is primarily a negative regulator of Th2-mediated airways hyper-reactivity (AHR) but can promote pulmonary granuloma formation and subsequent lung parenchymal damage. Thus, IL-18 expression is enhanced in pulmonary infiltrates in sarcoidosis patients [176], whereas reduced levels are found in asthmatic subjects [177]. IL-18 is detected at significantly reduced levels in bronchoalveolar lavage fluid and in alveolar macrophage cultures derived from asthmatic donors compared with healthy controls.…”

Genetics of Sarcoidosis: Candidate Genes and Genome Scans

“…BALF and serum IL-18 levels are increased in sarcoidosis (71). An association between IL-18607 (A/C) polymorphism and sarcoidosis has been reported and refuted in Japanese (72,73) and white subjects (74,75).…”