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.

The aim of the present study was to investigate the correlation between tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-12p40-containing cytokines, in silicosis patients and healthy donors exposed to silica dust, in an attempt to clarify the reason for variety of clinical outcomes between humans with similar exposure history. Serum levels of TNF-alpha, IL-12p40, IL-12p70 and IL-23 in total group of 62 silicosis patients, 24 healthy donors with similar exposure history like patients and 19 healthy donors without exposure were determined by enzyme-linked-immunosorbent assay (ELISA) method. The serum level of TNF-alpha was significantly higher in healthy donors exposed to SiO(2) (22.4 +/- 11.1 pg/mL) in comparison with non-exposed healthy donors (14.8 +/- 8.8 pg/mL; p = 0.022) and similar to that in silicosis patients. In total, group of silicosis patients significantly elevated levels of TNF-alpha (20.9 +/- 12.9 vs. 14.8 +/- 8.8 pg/mL; p = 0.047) and IL-12p40 (94.5 +/- 51.6 pg/mL vs. 68.7 +/- 26.2 pg/mL; p = 0.029) compared to non-exposed healthy donors were observed. In addition, a strong positive correlation between TNF-alpha and IL-23 levels (r = 0.678; p = 0.022) and between TNF-alpha and IL-12p70 levels (r = 0.75; p = 0.0003) was detected in the group of exposed healthy donors, while in the group of silicosis patients, a significant positive correlation was observed only between TNF-alpha and IL-12p40 (r = 0.434; p = 0.00048), in contrast to other IL-12p40 containing cytokines. In conclusion, we could assume that the elevated serum levels of TNF-alpha are associated with exposition to silica particles, while the elevation of both TNF-alpha and IL-12p40 is associated with silicosis development and severity. Additionally, the balance between IL-12p40-containing cytokines may also contribute to the silicosis progression.

To assess the role of IL-12Bpro and GSTP1 polymorphisms on induced interleukin (IL)-12p40 production in respect to silicosis development, we examined their distribution in 63 silicosis patients and 165 healthy donors. Decreased frequencies of IL-12Bpro-2 allele (42% vs 62.5%, P = 0.0042) and genotype 22 (19% vs 40%, P = 0.02) in patients compared with exposed healthy donors suggested their protective role in silicosis susceptibility. The GSTP1 A/G polymorphism was also associated with silicosis susceptibility. The allele G and genotype GG were overrepresented among patients than among healthy men (36% vs 23%, P = 0.013; 14% vs 2%, P(c) = 0.012). Also, patients' peripheral blood mononuclear cell (PBMC) produced higher IL-12p40 than healthy donors' depending on both IL-12Bpro and GSTP1 polymorphisms. In conclusion, homozygosity of high producer IL-12p40 genotype IL-12Bpro-11 and GSTP1-GG had the highest genetic risk of silicosis development in Bulgarian miners.

AbstractThe study was conducted among 92 male workers, divided into two groups depending on workplace and level of inorganic dust containing free crystalline SiO2 in the work environment, and 43 healthy workers without exposure to dust aerosols. The measured inhalable and respirable dust concentrations, as well as the concentration of free crystalline silica (FCS) in the respirable fraction were different for the two groups, but the percentage of free crystalline silica in the respirable fraction was almost identical. Significantly higher neopterin levels were found in workers exposed to dust, compared to the control group: 12.72 nmol/L and 6.32 nmol/L respectively (p<0.05). No significant difference was found between serum neopterin levels in both groups of the exposed workers. Among the groups with different length of service, a statistically higher neopterin level was evident only in the workers with length of service less than 10 years (p<0.05). The correlation analysis did not find a significant dependence of neopterin levels on the age of the studied workers or on the duration of smoking in packet years. The difference between neopterin levels in smokers and non-smokers was nonsignificant. The results obtained show that increased neopterin levels in the exposed workers are not influenced by individual features, duration and level of exposure to inorganic dust, but mostly by the presence of FCS in the respirable fraction.

It has been well defined that obesity is strongly linked with several respiratory symptoms and diseases, but no convincing evidence has been provided for chronic obstructive pulmonary disease (COPD). In the current study, we aim to assess the possible prevalence of obesity in patients with COPD in a cross-sectional case-control study of individuals from the region of Stara Zagora, Bulgaria, and to explore whether the body mass has some effect on the lung function of COPD patients. The study included 158 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) II, III, and IV stages) and 123 individuals unaffected by the disease (control). A higher frequency of obesity compared to the controls (20.3%) was observed in patients with COPD (29.1%, p=0.093), especially in those with GOLD II stage (37.7%, p=0.009). Prevalence of obesity was highest in COPD GOLD II, followed by GOLD III and IV stages (p=0.068). When diabetes was considered as confounding factor, we found a significant prevalence of obesity in COPD patients than the controls with diabetes (p=0.031). Interestingly, there was a statistically significant moderate positive correlation between the body mass index and forced expiratory volume in one second as a percentage of predicted value in the whole patients' group (R=0.295, p=0.0002) as well as in the subgroups of GOLD II (R=0.257, p=0.024) and GOLD III COPD (R=0.259, p=0.031).The results of our study propose that the increased body mass, particularly obesity is frequent comorbidity to COPD, especially to less severe diseases. Moreover, the results suggest that the higher body weight may provide some protection against the impairment of lung functions in patients with stable COPD.