Pulmonary sarcoidosis: patterns of cytokine release in vitro

Abstract

This study was designed to investigate the ability of bronchoalveolar and blood mononuclear cells to produce inflammatory mediators in vitro in pulmonary sarcoidosis. Seventeen patients with pulmonary sarcoidosis (stage I n=8; stage II/III n=9) and 10 normal controls were investigated. Bronchoalveolar and peripheral blood mononuclear cells were cultured in serum-free medium, without stimulant, for 24 h, and the supernatants analysed for concentrations of interleukin (IL)-1β (IL-1β), IL-2, IL-6, tumour necrosis factor-α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ) and neopterin.Bronchoalveolar lavage cells (BALC) of sarcoid patients released significantly higher amounts of TNF-α, IL-6, IFN-γ and neopterin in comparison to normal controls. When smokers were excluded, there was also an increased release of IL-1β and GM-CSF. In the sarcoid group, the levels of IL-1β, IL-6, TNF-α and GM-CSF showed highly significant correlations between each other, but not with IL-2, IFN-γ or neopterin. Sarcoid patients whose BALC released more TNF-α or GM-CSF had higher percentage counts of alveolar macrophages but fewer lavage lymphocytes. In sarcoid patients, peripheral blood mononuclear cells (PBMNC) also released higher amounts of IL-1β, TNF-α, IL-6 and GM-CSF but less neopterin than normal controls. Patients whose PBMNC produced more IL-1β, IL-6 and GM-CSF had higher absolute and relative lavage neutrophil counts. No relationships were observed between cytokine release and radiographic or physiological markers of disease severity.We conclude from this study that sarcoid inflammation is associated with an increased and concerted release of monocyte/macrophage-derived cytokines not only in the lung but also in the peripheral blood. We speculate that the lymphokines, IFN-γ and IL-2, are not the primary triggers.

Cytokine mRNA gene expression in active and nonactive pulmonary sarcoidosis

“…Lymphocytic alveolitis is an early initiating event in the formation of granulomatous lesions [12,18], and it is well established that there is a compartmentalization of T-lymphocytes, especially CD4+ cells, within the lungs of individuals with pulmonary sarcoidosis [13,[18][19][20][21][22]. Our data indicate that there is an increase in the number of BAL cells expressing IL-2 and IFN-γ mRNA in sarcoidosis.…”

“…Indeed, numerous studies have shown that analysis of peripheral blood fails to give a true picture of the character and magnitude of immune processes within the lung [3,5,12,13,[18][19][20][21][22]. This has been particularly evident when comparing the profile of cytokine expression within the peripheral blood and BAL fluid of individuals with sarcoidosis [3,5,13,22]. Since cells recovered by BAL have been shown to accurately reflect the alveolitis of lung diseases, including sarcoidosis [17], we chose to examine a wide range of cytokines in the local milieu as a means of investigating the histopathology of clinical activity.…”

Airway dendritic cell phenotypes in inflammatory diseases of the human lung

“…In patients with sarcoidosis, a specific increase in CD1a-negative mDC numbers within the airways was observed. Interestingly, sarcoidosis is associated with enhanced production of interleukin-1 and -6 and TNF-a [22,23]. Thus, the observed increase in CD1a-negative mDCs might contribute to this cytokine profile.…”

Transforming growth factor-beta1 in sarcoidosis

“…In a recent study, PRIOR et al [17] did not demonstrate any significant correlation between the release of in vitro cytokines by BAL cells and the clinical indices comprising pulmonary function in sarcoidosis. In the present study, an increased level of TGF-β 1 was demonstrated in BAL fluid but not in AM supernatants from patients with altered lung function compared with patients with normal lung function.…”