Interleukin-1 Beta Gene Research Articles

THE DISACCHARIDE TREHALOSE INHIBITS PROINFLAMMATORY PHENOTYPE ACTIVATION IN MACROPHAGES AND PREVENTS MORTALITY IN EXPERIMENTAL SEPTIC SHOCK

Proinflammatory phenotype activation in macrophages (MPhis) after sepsis orchestrates an inflammatory response leading to multiple organ dysfunction. Trehalose preserves cell viability during exposure to a range of environmental stresses. We investigated whether trehalose may inhibit endotoxin-induced activation of the inflammatory phenotype in MPhis. Rat peritoneal MPhis were stimulated with 50 microg/mL of Salmonella enteritidis lipopolysaccharide (LPS). Stimulated MPhis were coincubated with trehalose (25, 50, and 100 mmol), sucrose (100 mmol), or RPMI alone. Macrophages cultures were used for Western blot analysis of extracellular-regulated kinase, c-jun-N terminal kinase, and inducible nitric oxide synthase; interleukin (IL) 1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) gene expression by real-time reverse transcriptase-polymerase chain reaction, and supernatants for measuring the release of inflammatory cytokines and nitrite content. In vitro trehalose significantly blunted LPS-induced extracellular-regulated kinase (LPS = 21 +/- 6 integrated intensity; LPS + trehalose 100 mmol = 2 +/- 0.3 integrated intensity), c-jun-N terminal kinase (LPS = 15 +/- 5 integrated intensity; LPS + trehalose 100 mmol = 3.5 +/- 0.9 integrated intensity), and inducible nitric oxide synthase activation (LPS = 12 +/- 3 integrated intensity; LPS + trehalose 100 mmol = 1 +/- 0.09 integrated intensity), blunted IL-1beta (LPS = 5 +/- 1.9 n-folds/beta-actin; LPS + trehalose 100 mmol = 1.5 +/- 0.8 n-folds/beta-actin), IL-6 (LPS = 4 +/- 1.5 n-folds/beta-actin; LPS + trehalose 100 mmol = 1.4 +/- 0.5 n-folds/beta-actin), and TNF-alpha (LPS = 4.2 +/- 1.6 n-folds/beta-actin; LPS + trehalose 100 mmol = 1.1 +/- 0.7 n-folds/beta-actin) gene expression, and markedly reduced the release of inflammatory cytokines and nitrite content. Furthermore, in vivo trehalose prevented mortality in rats challenged with a lethal dose (20 mg/kg; LD90) of LPS (80% survival rate and 70% survival rate 24 and 72 h after LPS injection, respectively) and reduced serum TNF-alpha. Sucrose did not modified inflammatory phenotype in vitro nor in vivo protected against endotoxin-induced mortality. Our study suggests that trehalose inhibits proinflammatory phenotype activation in MPhis and prevents endotoxin-induced mortality.

Pharmacogenomics of Antidepressant Medications

With the completion of the human genome project, surges in studies investigating the association of antidepressant responsiveness and select polymorphisms have been conducted. Studies have been completed investigating polymorphisms in the monoaminergic system, including the serotonin transporter gene, the serotonin 1A, 2A, and 6 receptor genes, the G-protein-coupled receptor genes, the tryptophan hydroxylase 1 gene, the monoamine oxidase gene, the dopamine receptor genes, and the noradrenergic genes. Other genes of potential interest for investigation include the nitric oxide gene, the angiotensin-converting enzyme gene, the interleukin-1 beta gene, the stress hormone system, and the phosphodiesterase genes. Many of the studies have provided positive results, but the studies are small and are limited to a specific ethnicity. Further research is needed in the area before an array of genes can be used to predetermine response to antidepressant medication.

Interleukin-1β gene (IL-1B) and interleukin 1 receptor antagonist gene (IL-1RN) polymorphisms and gastric cancer risk in an Omani Arab population

Gastric cancer (GC) is the most common malignancy in Oman. Interleukin-1beta gene (IL-1B) and interleukin-1 receptor antagonist gene (IL-1RN) polymorphisms have been associated with increased GC risk. No previous studies have examined their role in an Arab population. We tested the associations between polymorphisms of IL1B at positions -31, -511, and +3954 and the IL-1RN polymorphism [variable number of tandem repeats (VNTR) and TC polymorphism at the -2018 position] and GC in Omani Arab patients. Genomic DNA was extracted from peripheral blood of 245 control subjects and 118 gastric cancer patients. The DNA samples were analyzed using the TaqMan allelic discrimination test for IL-1B -31, -511, and +3954 polymorphisms and IL-1RN -2018 polymorphism. The VNTR of IL-1RN was genotyped using the polymerase chain reaction followed by agarose gel electrophoresis. There was an association between the presence of IL-1RN*2 allele and gastric cancer [odds ratio (OR) = 2.2, 95% confidence interval (CI) = 1.0-3.3, P = 0.04). The GC risk further increased to OR = 3.5 (95% CI = 1.0-11.9) in Helicobacter pylori-positive patients. No association was found between any of the other polymorphisms studied and GC. IL-1RN polymorphism increased the risk of GC in an Omani Arab population, consistent with previous reports. In contrast, the IL-1B -31 polymorphism was not associated with an increased GC risk. These findings underscore the role of cytokine gene polymorphisms in the development of GC and further support the ethnic differences in the effect of IL-1B polymorphism on GC carcinogenesis.

Research on relationship between gene polymorphisms of interleukin-1 family and endometriosis

To investigate whether interleukin-1 beta (IL-1beta ) and interleukin-1 receptor antagonist (IL-1RA) gene polymorphisms are associated with endometriosis (EMs) in Chinese women. One hundred and thirty-eight patients with EMs and 100 women without EMs were enrolled in the study. Polymorphisms for IL-1 beta-511 promoter, IL-1 beta exon 5, and IL-1RA were detected by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). There were no significant differences about the distribution of the genotypes and alleles of IL-1 beta -511 promoter and IL-1 beta exon 5 in two groups (P > 0.05). The frequencies of A1/A1, A1/A2, A1/A4 and A2/A2 of IL-1RA gene were 84.1 %, 12.3 %, 2.9 % and 0.7 % in EMs and 95 % , 4 % ,1 % and 0 % in controls, respectively (P=0.042). The A1, A2 and A4 alleles were 91.7 % , 6.9 % and 1.4 % in EMs and 97.5 % , 2 % and 0.5 % in controls (P=0.019). In comparison with the reference genotype, the wild A1/A1 homozygote, the odds ratio for A1/A2 was 3.48 (95 % CI: 1.13 - 10.69). Compared with the A1 allele, the odds ratio for the A2 allele was 3.66 (95 % CI: 1.23 - 10.94). Association between the IL-1 beta-511 promoter,IL-1 beta exon 5 polymorphisms and EMs in China is not found. However, the A2 allele of IL-1RA gene may be one of the risk factors for the Chinese women in Zhejiang Province to suffer EMs.

Multiple strand displacement amplification of DNA isolated from human archival plasma/serum: Identification of cytokine polymorphism by pyrosequencing analysis

BackgroundDNA isolation from formalin-fixed paraffin-embedded tissue appears to be problematic due to degradation caused by fixative. Our aim was to investigate if the isolated genomic DNA from archival plasma/serum, combined with multiple strand displacement amplification (MDA) can be used for genotyping. MethodsNine archival plasma/serum samples and freshly frozen gastric biopsies from the same nine H. pylori-infected subjects were used for DNA isolation. Subsequently, MDA-DNA derived from the plasma/serum samples and DNA isolated from the antrum biopsies were analyzed by PCR amplification and pyrosequencing for the presence of interleukin-1beta gene (IL-1B) single nucleotide polymorphism (SNP). In addition, Southern blot and pyrosequencing analysis of H. pylori-specific PCR amplicons were performed. ResultsIL-1B SNP profiles obtained from the plasma/serum MDA-DNA and antrum biopsy DNA were identical. A C/C genotype was observed in 7 of 9 samples, and 2 of 9 revealed a C/T genotype for IL-1B −511. Similarly, 7 of 9 had a T/T, and 2 of 9 had a C/T genotype for IL-1B −31; 4 of 9 had a C/C, 4 of 9 had a C/T, and 1 of 9 had a T/T genotype, respectively, for IL-1B +3954. Moreover, pyrosequencing analysis revealed the presence of H. pylori 26695 and J99-like 16S rDNA variable V3 region sequence motifs in the antrum biopsies but not in the plasma/serum samples. ConclusionsWe conclude that MDA combined with pyrosequencing enables a rapid and accurate molecular typing of cytokine single nucleotide polymorphisms from archival plasma/serum samples.

Interleukin-1 alpha but not interleukin-1 beta gene polymorphism is associated with polycystic ovary syndrome

Interleukin-1 (IL1) is a multifunctional cytokine and IL1-mediated inflammatory processes have been proposed to influence the processes of ovulation, fertilization and implantation. All these parameters are also affected in women with polycystic ovary syndrome (PCOS). This study investigated the association of common polymorphisms of the interleukin-1 genes (IL1A and IL1B) with the occurrence and clinical characteristics of PCOS. We evaluated one polymorphism of the IL1α gene (IL1A C[−889]T) and two of the IL1β gene (IL1B promoter C[−511]T and IL1B exon 5 position +3953) in 105 Caucasian women with PCOS and 102 healthy Caucasian controls by polymerase chain reaction. For the mutated IL1A allele, allele frequencies in women with PCOS and controls were 60% and 46%, respectively, versus 40% and 54%, respectively, for the wild type allele. Allele frequencies in women with PCOS and controls were 59% (54%) and 61% (41%), respectively, for the mutated IL1B promoter (mutated IL1B exon 5) and 41% (46%) and 39% (59%), respectively, for the wild type alleles. Presence of a polymorphism in the interleukin-1α but not the interleukin-1β gene was found to correlate with the occurrence of PCOS (p=0.04; odds ratio 1.8). The serum level of FSH and subsequent LH/FSH ratio correlated with the polymorphism of IL1A within the PCOS group (p=0.005 and 0.01, respectively). We have shown that a common polymorphism of the interleukin-1α but not interleukin-1β gene is associated with the presence of PCOS and with clinical parameters of women affected by this condition.

Geldanamycin Interferes with the 90-kDa Heat Shock Protein, Affecting Lipopolysaccharide-Mediated Interleukin-1 Expression and Apoptosis within Macrophages

We have demonstrated that lipopolysaccharide (LPS)-mediated reactive oxygen species (ROS) and signal transduction are involved in the regulation of interleukin-1 (IL-1) beta gene expression within macrophages. Because the 90-kDa heat shock protein (Hsp90) plays an important role in the LPS mediation of macrophage activation, using Hsp90 inhibitor geldanamycin A (GA), we analyzed the mechanism of Hsp90 upon LPS-transduced signaling in the regulation of IL-1 expression and determined the function of Hsp90 regarding the viability of human primary macrophages and murine macrophages cell line. In essence, GA decreased LPS-induced Hsp90/pp60Src heterocomplex formation. In addition, Hsp90 is important for IL-1 protein translation, plays a minor role in IL-1 mRNA transcription, and is involved in nuclear factor-kappaB activation and the phosphorylation and activation of p38, c-Jun NH2-terminal kinase, and extracellular signal-regulated kinase; however, Hsp90 plays a more important role in LPS-stimulated p38 activation. In analyzing the function of Hsp90 regarding the cytotoxicity/viability of macrophages, we found that the combination of LPS and GA increases apoptosis, as evidenced by the increased caspase-3 activity and the proportion of nuclear/chromatin condensation. In contrast, N-acetyl-cysteine dramatically blocked GA/LPS-induced ROS production, simultaneously decreasing caspase-3 activity and the presence of apoptotic nuclei. We concluded that Hsp90 plays an indispensable role in the process of LPS-induced IL-1 secretion. Furthermore, we established the mechanism of GA interference with Hsp90 function for LPS-stimulated macrophages, resulting in increased ROS production and caspase-3 activation, and consequently leading to synergistic enhancement of macrophage apoptosis.

Genetic polymorphisms of interleukin‐1‐beta in association with sustained response to anti‐viral treatment in chronic hepatitis B in Chinese

Interleukin-1beta is a pro-inflammatory cytokine that may influence host defence against viral infection. To investigate the impact of interleukin-1beta gene polymorphism on the response to anti-viral treatment. Hepatitis B e antigen-positive chronic hepatitis B patients who have completed a randomized study of peginterferon alpha-2b and lamivudine combination vs. lamivudine monotherapy were included. Sustained responders were patients who had persistent hepatitis B e antigen loss and less than two occasions with hepatitis B virus DNA >100 000 copies/mL at any time up to week 76 post-treatment. Polymorphisms at interleukin-1beta-511, -31 and -3954 and interleukin-1 receptor antagonist (RN) were studied. Eighty-eight patients were studied and 18 (20%) patients developed sustained response. Near complete linkage disequilibrium was observed between interleukin-1beta-511 and -31 loci. After adjustment for the potential confounding effects of treatment allocation, hepatitis B virus genotype, pre-treatment alanine aminotransferase and hepatitis B virus DNA levels, genotype C/T at interleukin-1beta-511 was found to be associated with higher sustained response than genotype C/C (adjusted odds ratio 10.4, 95% CI 1.1, 96.9, P = 0.040). The proportion of sustained responders tend to be higher among patients with allele T at interleukin-1beta-511 (83%) than those without (70%) (P = 0.058). High interleukin-1beta production genotype at position -511 has a favourable response to anti-viral treatments.

Alkali-Soluble Polysaccharides of Rhizoclonium riparium Alga Induce IL-1 Gene Expression via Protein Kinase Signaling Pathways

Fortification of aquaculture foodstuff with various algae may improve the resistance of certain fish or shrimp to diseases and, as a routine procedure, has become ever more popular and, seemingly, important. Herein, we isolated certain alkali-soluble polysaccharides from a Rhizoclonium riparium alga (RASP), polysaccharides that can be separated into two different groups on the basis of the polysaccharide's molecular weight. Using gas chromatography-mass spectometry analysis, we found that the major monosaccharides constituting the higher molecular-weight group of RASP were galactose (41.99%), glucose (34.53%), xylose (20.24%), and mannose (3.24%). Using a murine-derived macrophage cell line J774A.1, we found that polysaccharide constituents of the higher molecular-weight group of RASP were able to induce interleukin-1beta (IL-1) gene expression via protein kinase-mediated signal transduction pathways. In essence, we found that c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38), but not extracellular signal-regulated kinase (ERK), play an important role in the regulation of IL-1 gene expression in RASP-stimulated J774A.1 cells. To the best of our knowledge, this is the first occasion that polysaccharides from R. riparium have been demonstrated to exert immunomodulation properties by the induction of IL-1 within macrophages. Our current results provide support for the possible use of R. riparium as an additive to various food/foodstuff, to modulate the immune response of humans or certain animals.

The Association Between the Interleukin-1 Polymorphisms and Gastric Cancer Risk Depends on the Family History of Gastric Carcinoma in the Study Population

The association between interleukin-1 polymorphisms, H. pylori and increased gastric cancer risk remains controversial. To compare the prevalence of these polymorphisms in individuals with two mutually exclusive diseases connected with infection, gastric cancer, and duodenal ulcer. 121 gastric cancer and 119 duodenal ulcer patients. Genomic DNA was typed for polymorphisms at position -511, -31 in the interleukin-1beta gene (IL-1 beta) using primer extension and mass-spectrometry. Analysis of the variable number of tandem repeats in intron 2, in its receptor antagonist gene (IL-1RN) was performed by PCR and agarose gel electrophoresis. All subjects were successfully genotyped for the three gene loci. IL-1 beta-511 was found to be in reverse linkage disequilibrium with IL-1 beta-31. The differences between gastric cancer and duodenal ulcer patients concerned only heterozygous variant of IL-1beta and were related to family history of gastric cancer, tumor stage, histology, site. Thus, CT carriers were found to have a higher risk of sporadic [OR 2.21 (95% CI, 1.22-3.99)], early [OR 2.81 (95% CI, 1.14-6.93)], diffuse [OR 2.48, (95% CI 1.21-5.09)] or non-cardia gastric cancer [OR 1.88 (95% CI 1.06-3.33)]. Furthermore, CT genotype was significantly more prevalent in gastric cancer patients with negative than in those with a positive family history (p = 0.039). The association between the interleukin-1 polymorphisms and gastric cancer risk depends on the family history of gastric carcinoma in the study population. This phenomenon may be in part responsible for differences in results of interleukin-1 studies performed on populations with low and high gastric cancer prevalence.

Association of Interleukin-1beta Gene Polymorphisms with Precancerous Gastric Lesions in African Americans and Caucasians

Interleukin-1beta plays an important role in inflammation and gastric physiology. Polymorphisms of the IL1B gene have been associated with gastric atrophy and increased cancer risk, especially in Helicobacter pylori-infected subjects. The aim of this study was to evaluate the relationship between IL1B and IL1 receptor antagonist gene polymorphisms and the risk of multifocal atrophic gastritis in African Americans and Caucasians. Genomic DNA was extracted from gastric biopsies of 269 adult outpatients (172 African Americans and 97 Caucasians) undergoing diagnostic upper gastrointestinal endoscopy. Histological diagnosis was evaluated according to the updated Sydney System and H. pylori status was assessed by Steiner silver stain. Polymorphisms of the IL1B gene (-511, -31, and +3954) and the IL1 receptor antagonist were investigated by PCR-RFLP. Logistic regression models were used to identify variables associated with multifocal atrophic gastritis in terms of odds ratios and 95% confidence intervals. Considering subjects with normal histology and nonatrophic gastritis as controls, a significant association was found between IL1B+3954T carrier and multiatrophic gastritis (OR 2.23, 95% CI 1.28, 3.88). Analyses stratified by ethnic group demonstrated similar associations in both African Americans (OR 2.23, 95% CI 1.14, 4.37) and Caucasians (OR 2.04, 95% CI 0.74, 5.65). A positive but not significant association was found between the allele 2 of the IL1RN and the presence of multifocal atrophic gastritis. The remaining proinflammatory polymorphisms were not associated with this precancerous lesion. Our results suggest that the presence of IL1B+3954T allele is a risk marker for multifocal atrophic gastritis in the population studied.

Distinct association of gene polymorphisms of estrogen receptor and vitamin D receptor with lumbar spondylosis in post-menopausal women

Contribution of genetic backgrounds to the etiology of lumbar spondylosis has been suggested by epidemiological studies. This study was designed to determine the association of restriction fragment length polymorphisms (RFLPs) of estrogen receptor (ER), vitamin D receptor (VDR), parathyroid hormone (PTH) and interleukin-1beta (IL-1beta) genes with the radiological severity of lumbar spondylosis at the disk level from L1/2 to L5/S1 in Japanese post-menopausal women. ER and VDR RFLP haplotypes were associated with the severity of spondylosis in the upper levels (L1/2 and L2/3) more than in the lower levels. Association of ER genotype was more pronounced in the group younger than average than in the older group, while that of VDR genotype was more significant in the older group. Neither PTH nor IL1-beta RFLP was associated with the severity at any levels in either stratified group. We thus conclude that ER and VDR genes may contribute to lumbar spondylosis in a distinct manner: estrogen sensitivity influences the severity in the early phase after menopause while vitamin D plays an important role at older ages when the contribution of estrogen loss is weaker.

Association between interleukin-1β-511C/T polymorphism and reflux esophagitis in Japan

Interleukin-1beta (IL-1beta) gene polymorphisms are related to hypochlorhydria and increase the risk of gastric cancer in the presence of Helicobacter pylori infection. However, little information is available about the genetic risk factors of reflux esophagitis. In this study we investigated its association with the IL-1beta polymorphisms. We examined 48 patients with reflux esophagitis and 96 control subjects, 89 with gastric cancer. IL-1beta-511C/T genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The frequency of IL-1beta-511T alleles was significantly higher in reflux esophagitis patients (57.3%) than in controls (41.1%) (P = 0.0215, chi(2) = 5.289). The frequency of IL-1beta-511T/T genotypes was also significantly higher in reflux esophagitis patients (31.3%) than in controls (15.6%). The odds ratio and the 95% confidence interval were 4.000 and 1.393-11.486, respectively. The frequency of IL-1beta-511T/T genotypes was significantly higher in reflux esophagitis patients (31.3%) than in gastric cancer patients (21.4%). The odds ratio and the 95% confidence interval were 2.961 and 1.054-8.316, respectively. IL-1beta-511T was associated with reflux esophagitis having hyperacidity. Differences of genetic background regarding gastric acid secretion may exist between Japanese and Caucasians.

Role of p38 mitogen-activated protein kinase in the pathogenesis of stress ulcer

To determine whether the activation of p38 mitogen-activated protein kinase (MAPK) is involved in the pathogenesis of stress ulcer. Model of stress ulcer was established with the treatment of rats with water-immersion restraint (WIR) stress. Ulcer index (UI) was macroscopically evaluated as a parameter of gastric mucosal lesions. Expression of phospho- and pan-p38 in gastric mucosa was detected using Western blot analysis. Tumor necrosis factor-alpha (TNF-alpha) and Interleukin 1beta (IL-1beta) gene expressions were analyzed by Northern blot analysis. As indicated in some experiments, rats were pretreated with intravenous injection of the specific p38 MAPK inhibitor CNI-1493 prior to WIR stress and then the changes of UI and TNF-alpha and IL-1beta mRNA expression were examined. The p38 MAPK was persistently activated in the gastric mucosa of rats with WIR stress, with maximal activation after 1 h of stress [(6.8 +/- 3.2) fold of baseline levels, P < 0.01]. Inhibition of p38 MAPK activation with CNI-1493 led to a marked decrease in UI in WIR stress rats. Similarly, the increased gene expression of proinflammatory cytokines TNF-alpha and IL-1beta in gastric mucosa induced by WIR stress were significantly diminished by p38 MAPK inhibition. p38 MAPK might have an important role in the pathogenesis of stress ulcer.

Association of cytokine and DNA repair gene polymorphisms with hepatitis B-related hepatocellular carcinoma

Hepatitis B virus (HBV) induces hepatocellular carcinoma (HCC) mainly by causing chronic necroinflammatory hepatic disease. We investigated the mechanisms underlying the inflammatory hepatocarcinogenesis by examining whether genetic variations in cytokines, antioxidant enzymes, and DNA repair genes affect the HCC risk. We analyzed 10 polymorphisms in the genes for interleukin-1beta (IL-1B), interleukin-1-receptor antagonist (IL-1RN), tumor necrosis factor-alpha (TNF-A), glutathione S-transferase, XRCC1, hMLH1, and XPD in 577 HBV carriers with HCC and 389 HBV carrier controls. Overall, only the hMLH1-93*A allele significantly increased HCC risk. We identified polymorphism combinations associated with HCC. In the presence of the IL-1RN*2 allele, adjusted odds ratios (ORs) for HCC associated with C/C, T/C, and T/T genotypes of the IL-1B-31 polymorphism were 1.00, 2.93 [95% confidence interval (95% CI) 1.07-8.07], and 5.76 (95% CI 1.79-18.53), respectively. There was a dose-dependent association between the number of putative high-risk genotypes in the IL-1B, TNF-A, hMLH1, and XRCC1 genes and HCC. The adjusted OR for HBV carriers with > or = 3 putative high-risk genotypes was 9.29 (95% CI 2.90-29.75) compared with those with none or only one of the high-risk genotypes. These associations were not observed among HBV carriers without the IL-1RN*2 allele. Smoking modified the combined effect of multiple loci in the IL-1RN, IL-1B, TNF-A, hMLH1, and XRCC1 genes; a high-risk multilocus genotype only significantly increased the risk in smokers (adjusted OR 4.84; 95% CI 1.69-13.92). Genetic variations in cytokine and DNA repair genes contribute to susceptibility to HBV-related HCC. Smoking increased such genetic susceptibility.

The IL-1 gene family and bone involvement in celiac disease

Celiac disease (CD) is associated with decreased bone mineral mass. Its pathogenesis is multifactorial since both systemic and local mechanisms may play a role. Our objective was to determine whether single-nucleotide polymorphisms in genes encoding members of the interleukin-1 family are associated with bone damage measured by densitometry in a series of 71 adult CD patients assessed at diagnosis. When compared with non-carrier CD patients, carriers of allele T of the interleukin-1beta gene (IL1B-511T) had a significantly lower bone mass at the total skeleton level (p = 0.0484) and a greater prevalence of osteopenia/osteoporosis (p = 0.0102). To our knowledge, this is the first evidence on the association between a genetic predisposition and low bone mass in CD patients. This finding supports the postulated inflammation-associated bone loss pathogenesis as one of the causes of bone weakness in CD.

Association between interleukin-1 beta (IL-1β) gene polymorphism and outcome after head injury: an early report

Recent studies focusing on the genetic influences on outcome after head injury (HI) have suggested that different alleles of certain genes are associated with different outcomes. Interleukin-1 beta (IL-1beta) gene, especially beta2 polymorphism, is frequently observed in Alzheimer's disease, a remarkable degenerative state in which HI is among the known risk factors. Therefore, the aim of this paper was to search for the possible association between the outcome and IL-1beta gene polymorphism in human HI. The study group was composed of the 69 patients admitted to the neurosurgery department after HI. The severity of the initial injury was evaluated by means of the Glasgow Coma Scale and outcome six months later was assessed by means of the Glasgow Outcome Scale. IL-1beta genotypes were determined from blood samples by standard methods. Fourteen of 25 (56%) patients with IL-1beta +3953 allele 2 had an unfavourable outcome (dead, vegetative state or severe disability) compared with eight of 44 (18.1%) patients without IL-1beta +3953 (p = 0.0004). Similarly, 20 of 28 (71.4%) patients with IL-1beta -511 allele 2 had an unfavourable outcome compared with two of 41 (4.8%) patients without IL-1beta -511 (p = 0.005). Patients who had a composite of IL-1beta 2/2 or 1/2 genotype from both -511 and +3953 region of the chromosome 2 were more prone to have bad prognosis. Results of our study demonstrated that there might be a significant association between IL-1beta gene polymorphism and outcome after HI, supporting the hypothesis of a genetically determined influence.

Association Between IL-1β Gene Polymorphism and Myocardial Infarction

HomeArteriosclerosis, Thrombosis, and Vascular BiologyVol. 25, No. 4Association Between IL-1β Gene Polymorphism and Myocardial Infarction Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBAssociation Between IL-1β Gene Polymorphism and Myocardial Infarction Yukihiko Momiyama, Reiko Ohmori and Fumitaka Ohsuzu Yukihiko MomiyamaYukihiko Momiyama First Department of Internal Medicine, National Defense Medical College, Saitama, Japan Search for more papers by this author , Reiko OhmoriReiko Ohmori First Department of Internal Medicine, National Defense Medical College, Saitama, Japan Search for more papers by this author and Fumitaka OhsuzuFumitaka Ohsuzu First Department of Internal Medicine, National Defense Medical College, Saitama, Japan Search for more papers by this author Originally published1 Apr 2005https://doi.org/10.1161/01.ATV.0000159700.18731.d2Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:e36To the Editor:We read with great interest the study by Iacoviello et al.1 They investigated IL-1β gene polymorphism (−511C/T) in 406 patients with myocardial infarction (MI) at young age and 419 controls and reported the TT genotype to be inversely associated with MI. Moreover, they demonstrated mononuclear cells with TT homozygote to show decreased IL-1β production compared with those with CC homozygote. They concluded that this polymorphism affects the risk of MI at young age.Inflammation plays an important role in atherosclerosis. Infectious agents, such as Chlamydia pneumoniae (CP), were often reported to be associated with MI. However, inflammatory responses to infection may vary from individual to individual, and only a small number of individuals develop MI. We previously investigated IL-1β (−511C/T) and IL-1Ra (a variable number repeat) gene polymorphisms and CP seropositivity in 292 patients undergoing coronary angiography.2 Notably, the IL-1 gene variants (IL-1β CC and/or IL-1Ra 2- or 3-repeat) were found to be associated with MI only in patients with CP seropositivity. Our report suggested that IL-1 gene polymorphisms modify the process of coronary artery disease (CAD) in patients with CP infection, leading to the development of MI. In the same line of evidence, the AtheroGene Group3 demonstrated that IL-6 (−174G/C) gene polymorphism was not a factor for CAD, but the association between infectious burden and CAD was modulated by IL-6 gene polymorphism.A recent large study4 investigated 112 polymorphisms in 4152 subjects. Only connexin (1019C/T), plasminogen activator inhibitor (PAI) (4G-668/5G), and stromelysin-1 (5A-1171/6A) gene polymorphisms were associated with MI, whereas IL-1β gene polymorphism was not.4 IL-1β gene polymorphism may not be a factor for MI in a general population, but it may play a role in the development of MI in certain individuals, such as in young subjects1 or subjects with CP infection.2 Large studies are important, but studies in certain subgroups, such as the study by Iacoviello et al1 and ours,2 will provide additional valuable information.1 Iacoviello L, Di Castelnuovo A, Gattone M, Pezzini A, Assanelli D, Lorenzet R, Del Zotto E, Colombo M, Napoleone E, Amore C, D’Orazio A, Padovani A, de Gaetano G, Giannuzzi P, Donati MB. Polymorphisms of the IL-1β gene affect the risk of myocardial infarction and ischemic stroke at young age and the response of mononuclear cells to stimulation in vitro. Arterioscler Thromb Vasc Biol. 2005; 25: 222–227.LinkGoogle Scholar2 Momiyama Y, Hirano R, Taniguchi H, Nakamura H, Ohsuzu F. Effects of interluekin-1 gene polymorphisms on the development of coronary artery disease associated with Chlamydia pneumoniae infection. J Am Coll Cardiol. 2001; 38: 712–727.CrossrefMedlineGoogle Scholar3 Georges JL, Rupprecht HJ, Blankenberg S, Poirier O, Bickel C, Hafner G, Nicaud V, Meyer J, Cambien F, Tiret L. Impact of pathogen burden in patients with coronary artery disease in relation to systemic inflammation and variation in genes encoding cytokines. Am J Cardiol. 2003; 92: 515–521.CrossrefMedlineGoogle Scholar4 Yamada Y, Izawa H, Ichihara S, Takatsu F, Ishihara H, Hirayama H, Sone T, Tanaka M, Yokota M. Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. N Engl J Med. 2002; 347: 1916–1923.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Fang Y, Xie H and Lin Z (2018) Association between IL-1β + 3954C/T polymorphism and myocardial infarction risk, Medicine, 10.1097/MD.0000000000011645, 97:30, (e11645), Online publication date: 1-Jul-2018. Rios D, Cerqueira C, Bonfim-Silva R, Araújo L, Pereira J, Gadelha S and Barbosa A (2010) Interleukin-1 beta and interleukin-6 gene polymorphism associations with angiographically assessed coronary artery disease in Brazilians, Cytokine, 10.1016/j.cyto.2010.02.012, 50:3, (292-296), Online publication date: 1-Jun-2010. April 2005Vol 25, Issue 4 Advertisement Article InformationMetrics https://doi.org/10.1161/01.ATV.0000159700.18731.d2PMID: 15790937 Originally publishedApril 1, 2005 PDF download Advertisement

Effects of IFN-α on the Inflammatory Response of Swine Leukocytes to Bacterial Endotoxin

Because low-dose interferon-alpha (IFN-alpha) treatment had proved effective in several models of chronic inflammation and autoimmune disease, a possible role of IFN-alpha in modulating the response of swine leukocytes to bacterial endotoxin was investigated in this study. Exposure of swine peripheral blood mononuclear cells (PBMC) to low concentrations of human IFN-alpha caused a strong, dose-dependent decrease in CD14 expression, the lowest level being observed at 5 U/ml IFN-alpha. This result was confirmed if PBMC were later exposed to purified lipopolysaccharide (LPS). A 10-fold lower IFN-alpha concentration (0.5 U/ml) caused the largest reduction of tumor necrosis factor-alpha (TNF-alpha) accumulation in the medium of pulmonary alveolar macrophages (PAM), stimulated with bacterial LPS. At 0.5 U/ml, the expression of the TNF-alpha gene in PAM was also strongly reduced, as opposed to cells pretreated with 50 U/ml IFN-alpha. In contrast, expression of the interleukin-1beta (IL- 1beta) gene was stimulated and that of the IL-6 gene was not significantly affected at both IFN-alpha concentrations. Results point to an important role of IFN-alpha in control of the inflammatory response to bacterial endotoxin in pigs.

Interleukin‐4 gene intron‐3 polymorphism is associated with transitional cell carcinoma of the urinary bladder

To evaluate whether polymorphism of the interleukin-4 gene exon 3, and of the interleukin-1beta gene exon 5 and promoter region, are associated with transitional cell carcinoma (TCC) of the urinary bladder, as cytokines are hypothesized to be important in cancer formation. The study included 138 patients with TCC of urinary bladder and 105 healthy controls living in the same area. Each genetic polymorphism was typed using polymerase chain reaction-based restriction analysis. Genotype distribution and allelic frequencies between patients and controls were compared. There were significant differences in genotype and allelic distribution of intron 3 RP1/RP2 polymorphism (P < 0.001), but no significant difference in genotype distribution or allelic frequencies of the interleukin-1beta gene polymorphism between patients with bladder cancer and controls. The interleukin-4 gene intron 3 polymorphism is associated with bladder cancer and is a potential genetic marker in screening for the possible causes of bladder cancer.