Among individuals with both asthma/atopy and the IL-6 -634 G allele, however, risk was increased at least 3-fold (OR = 3.1, 95% CI = 1.2-8.3 for all cancers and OR = 4.2, 95% CI = 1.5-11.6 for adenocarcinomas) relative to individuals with no asthma/atopy and the CC genotype.
Although a common, non-synonymous variant in the IL-6 receptor gene (IL6R rs2228145" genes_norm="3570">Asp358Ala; rs2228145 A>C) is associated with the risk of several common diseases, with the 358Ala allele conferring protection from coronary heart disease (CHD), rheumatoid arthritis (RA), atrial fibrillation (AF), abdominal aortic aneurysm (AAA), and increased susceptibility to asthma, the variant's effect on IL-6 signaling is not known.
Four functional IL6 single nucleotide polymorphisms (SNPs) and a nonsynonymous IL6R SNP were genotyped in 700 Mexican and Puerto Rican asthma families and in 443 African-American asthma cases and controls.
Cases showed significant higher frequency of the genotypes: IL-6-174 GG (P<0.05, OR=3.2, 95% CI=1.09-10) that was evident mainly in the uncontrolled asthma subgroup indicative of the possibility of being a severity genotype.
In conclusion, our studies led to identification of some key candidate genes, namely IRF2, IL6, IFNGR2, STAT4 and IL4RA that modulate genetic susceptibility to asthma in the Indian population.
Other inflammatory pathways are also emerging as implicated in asthma and COPD molecular phenotypes, including Type one and Type 17 adaptive immune responses and proinflammatory cytokines, such as interleukin-6.
Glucocorticoids activated the glucocorticoid receptor and inhibited serum-induced secretion of interleukin-6 in bronchial smooth-muscle cells from both subjects with asthma and those without asthma; however, glucocorticoids inhibited proliferation only in bronchial smooth-muscle cells from subjects without asthma.
MDM galectin-3 secretion was lower in asthma (9.99 (2.67, 15.48) ng/mL) compared with the healthy controls (20.72 (11.28, 27.89) ng/mL; p = 0.044) while IL-6 and CXCL8 levels were similar.
The group with both asthma and OSA had higher CRP, higher IL-6, a longer sleeping time in stage N1 sleep and stage N2 sleep, and less time in stage R sleep than the control group with no asthma or OSA.
Treatment of HASM cells with IL-6+sIL6R induced proliferation in a dose-dependent fashion, suggesting a role for IL-6 trans-signaling in asthma pathogenesis.
Taken together, our results indicate that IL-6 plays a pathogenic role in the HDM-induced asthma model and that lung macrophages and dendritic cells are the predominant sources of pathogenic IL-6 but contribute differently to the disease.
Airway smooth muscle (ASM) mass is increased in asthma, and ASM cells from patients with asthma are hyperproliferative and release more IL-6 and CXCL8.
The serum OX40L level showed a significant positive correlation with serum IgE, blood percentages of eosinophils and neutrophils, serum IL-6 and TSLP, and showed a negative correlation with asthma control test (ACT) score and forced expiratory volume in first second (FEV1%).
The airway epithelium is a major contributor to asthma pathology and has been shown to produce an excess of inflammatory and pro-remodelling cytokines such as TGF-β, IL-6 and IL-8 as well as deficient amounts of anti-viral interferons.