Association between polymorphisms of cytokine genes and secretion of IL-12p70, IL-18, and IL-27 by dendritic cells in patients with pulmonary tuberculosis

Abstract Proinflammatory cytokines are known to play a crucial role in the pathogenesis of tuberculosis, and gene polymorphisms in the promoter regions of cytokine genes were shown to substantially influence the secretory capacity of immune cells. In the present study, we analyzed the association between polymorphisms of the IL12B , IL18, and IL27 genes and the secretion of the proinflammatory cytokines IL-12р70, IL-18, and IL-27 by myeloid dendritic cells (mDCs) in pulmonary tuberculosis (PTB) patients. The study enrolled 334 patients with newly diagnosed infiltrative and disseminated PTB. Cultivation of mDCs was performed from non-proliferating progenitors of CD14 + blood monocytes. Cytokine secretion was evaluated by measuring cytokine concentration in the mDC culture supernatants using enzyme-linked immunosorbent essay (ELISA). To study cytokine gene polymorphisms, a polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP) were performed. Reduced secretion of IL-18 and IL-27 by mDCs in PTB patients was associated with 105A/C polymorphisms of the IL18 gene, and 2905T/G, 4730T/С, and −964A/G of the IL27 gene, respectively. Polymorphism IL12B/insertion had a bidirectional influence on the secretion of IL-12p70, being associated with decreased levels of the cytokine in infiltrative PTB and increased levels in disseminated PTB patients.