Interleukin-12B-3'UTR polymorphism in association with IL-12p40 and IL-12p70 serum levels and silicosis severity.

Susceptibility to silicosis and to disease severity is in part genetically determined. In this study, the role of IL-12B-3'UTR polymorphism in susceptibility and severity of silicosis and its influence on IL-12p40 and IL-12p70 serum level were investigated. The quantity of IL-12p40 and IL-12p70 was detected by enzyme-linked immunosorbent assay and the genotype of IL-12B was determined using the polymerase chain reaction-restriction fragment-length polymorphism method. We observed elevated IL-12p40 in contrast to IL-12p70 serum levels in a group of 62 silicosis patients compared with both control groups. In severe silicosis patients, we detected the highest IL-12p40 serum levels (129.1 +/- 67.7 pg mL(-1)); lower in patients with the moderate (94 +/- 41.6 pg mL(-1)), whereas in mild silicosis, the IL-12p40 levels (67 +/- 23.5 pg mL(-1)) was similar to these in healthy donors. According to IL-12B polymorphism, increased serum levels were observed in subjects with AA genotype (103.2 +/- 46.9 pg mL(-1)) compared to silicosis patients with AC genotype (82.7 +/- 38.3 pg mL(-1)). No significant differences of genotype and allele frequencies of the 3'UTR polymorphism were observed between silicosis patients and healthy controls. However, the heterozygous genotype was found approximately five times more frequently in patients with mild and moderate (48% and 52%) silicosis compared to patients with severe silicosis (11%), and that IL-12B polymorphism may contribute to silicosis severity rather than to susceptibility. Our data demonstrated that elevated serum IL-12p40, independently of IL-12p70 levels, is associated with severity of silicosis, and suggested that IL-12p40 profibrotic activity may contribute to silicosis severity.