As genetic factors have been implicated in its aetiology, in our study we investigated whether the promotor polymorphisms in three genes coding for inflammatory mediators interleukin-6 (IL-6), interleukin-12 (IL-12), and interleukin-18 (IL-18) could be associated with susceptibility to sarcoidosis.
In situ hybridization revealed different sites of expression in tuberculosis and sarcoidosis lungs, with AEC-II as one major source of IL-18 in the alveolar compartment.
Epithelial lining fluid from active sarcoids contained elevated levels of interleukin-18, interferon-gamma, and interleukin-12 compared with recovered patients and also contained significantly higher levels of endotoxin.
Expression of IL-18 and tumour necrosis factor-alpha (TNFalpha) mRNA in cells of the BAL of 23 patients with sarcoidosis and nine healthy volunteers was determined using semiquantitative RT-PCR.
IL-18 mRNA expression was observed in freshly isolated sarcoid BAL fluid cells as well as in LPS-stimulated sarcoid BAL fluid cells, but IFN-gamma and IL-12 mRNA expression was observed only in LPS-stimulated BAL fluid cells.
Our results coupled with those of previous investigations demonstrating activity of IL-18 in inducing interferon-gamma production suggest a significant role of IL-18 in the pathogenesis of sarcoidosis.
Similarly, constitutive expression of IL-18 protein was observed within the airway epithelium of control individuals, with more positive cells found within sarcoidosis tissue (p<0.01) and fewer within asthmatic tissue (p<0.01), compared to controls.