IL‐1α (− 889) promoter polymorphism is a risk factor for osteomyelitis

Abstract

As osteomyelitis (OM) induces the synthesis of inflammatory cytokines and IL-1 mediates bone resorption by osteoclasts we determined if there is an association between certain common polymorphisms of the genes encoding proinflammatory cytokines (IL-1 alpha and beta, IL-6, TNF-alpha) and OM in adults. The IL-1 alpha (-889) TT genotype was significantly more frequent among 52 OM patients than in 109 healthy controls (13/52, [25.0%] vs. 9/109, [8.3%], P = 0.0081, chi(2) = 7.01, OR = 3.7, 95% CI, 1.35-10.34). Patients who were homozygous for the T allele were younger than the rest of the OM patients (mean age 35.7 +/- 11.5 vs. 58.1 +/- 18.6 years, P = 0.001). IL-1 beta TT (+3953) polymorphism was also more frequent in OM patients (P = 0.014, chi(2) = 5.12, OR = 5.1, 95% CI, 1.21-52.14), but IL-1 beta is in linkage disequilibrium with the IL-1 alpha *T (P < 0.001). Route of infection, chronicity of the infection, type of microorganism isolated, and frequency of relapses were similar in patients with and without the IL-1 alpha TT genotype. There were no associations between OM and polymorphisms of other cytokines genes. IL-1 alpha serum levels were significantly increased in all the OM patients independently of their IL-1 genotype compared to the controls (P = 0.021). Although IL-1 alpha serum levels were not significantly higher in patients with the IL-1 alpha (-889) polymorphism, this does not exclude a difference in production of IL-1 alpha by osteoclasts or other inflammatory cells at the site of infection.

Microarray Analysis of Gene Expression Profiles in Response to Treatment with Melatonin in Lipopolysaccharide Activated RAW 264.7 Cells

“…These cytokines are synthesized by a variety of cell types, including activated macrophages, stimulated B lymphocytes, and fibroblasts, and are potent mediators of inflammation and immunity [22]. Moreover, IL1A and IL1B polymorphisms are associated with various inflammatory diseases, such as periodontitis, osteomeylitis, and Bowel disease [23][24][25]. In this study, IL1A and IL1B were highly up-regulated by LPS, but down-regulated by melatonin treatment.…”

Polymorphisms in Cytokine and Cellular Adhesion Molecule Genes and Susceptibility to Hematotoxicity among Workers Exposed to Benzene

“…For instance, the IL-1A (À889C>T) is in the 5V untranslated region, has been shown to produce a higher amount of IL-1A mRNA (38), and has been associated with autoimmune, degenerative, and infectious diseases (39,40). The IL-4 promoter SNPs and haplotypes are particularly interesting because of emerging studies that indicate that variation in the expression of this gene could affect a range of diseases such as severity of infection with respiratory syncytial virus in young children, asthma, atopy, fungal infection with Candida albicans in leukemia patients, and inflammatory bowel disease (41)(42)(43)(44); moreover, this same promoter SNP has been shown to increase reporter gene expression in vitro (41,42,45).…”

In Vivo Interleukin-6 Protects Neutrophils from Apoptosis in Osteomyelitis

“…Much attention has been dedicated to improving the surgical and medical treatment of osteomyelitis, but little progress has been made toward understanding its pathogenesis. It is clear that it is multifactorial and influenced mainly by local factors related to the bone lesion and microorganisms inoculated into the bone, but inherited factors and cell immunity dysfunctions could play some role as well (3,41).…”