儿童胃黏膜白细胞介素mRNA水平与幽门螺旋杆菌感染的研究

目的分析儿童胃黏膜白细胞介素(IL-1β)水平与幽门螺旋杆菌(H.pylori)及其高毒力亚型感染间的相关性。方法实时定量聚合酶链(real-time PCR)检测H.pylori的保守基因ure以判断H.pylori的感染,高毒力亚型基因vacA s1用real-time PCR检测,用PCR扩增另一高毒力基因cagA羧基端EPIYA基序所在区,然后测序确定其亚型。IL-1βmRNA使用PCR-荧光探针法检测,比较循环CT法分析。结果患儿中无论是低毒力还是高毒力的H.pylori感染都与胃黏膜IL-1βmRNA水平无显著相关性。结论 H.pylori对儿童胃黏膜IL-1β表达的影响作用并不明显,可能还有其他一些环境、遗传因素如IL-1基因簇多态性与H.pylori共同作用调节胃黏膜IL-1β的表达。     

胃癌低发区幽门螺旋杆菌感染、IL-1基因多态性和胃黏膜萎缩关系的研究

目的：探讨IL-1B-511基因多态性对幽门螺旋杆菌（H.pylori）感染后胃黏膜萎缩的影响。方法：（1）采用PCR-限制性长度片段多态性（restriction fragment length polymorphism，RFLP）分析法检测胃癌低发区广东省普通人群192例的基因型；（2）采用酶联免疫吸附法（ELISA）检测上述人群的且pylorl感染率、胃蛋白酶原Ⅰ（pepsinogen Ⅰ，PGI）、胃蛋白酶原Ⅱ（pepsinogen Ⅱ，PGD）和胃泌素（gastrin）的浓度。结果：H.pylori阳性者PGⅠ／PGⅡ显著低于Hpylori阴性者（P〈0．01），H.pylor4阳性的1L-1B-511T／T基因型者PGⅠ／PGⅡ比值显著低于C／C和C／T基因型者（均P〈0．05）。血清胃泌素浓度与IL-1B-511的基因型没有明确的关系（P〉0．05）。结论：在胃癌低发区，IL-1B-511基因型可能增加感染H.pylori后胃黏膜萎缩发生、发展的危险性。     

IL-1B和TNFα基因多态性与胃癌易感性的关系

目的探讨汉族人群中白介素1B-511、-31两个位点（IL-1B-511、IL-1B-31）和肿瘤坏死因子-308位点（TNFα-308）基因多态性与胃癌易感性之间的关系。方法采用荧光定量PCR方法，对178名胃癌患者及196名健康人进行基因分型，评价胃癌患者和健康对照组之间的基因分型。结果IL-1B的-511，-31两个位点基因多态性在胃癌患者和正常人之间的分布有明显差异（P=0.027），胃癌患者IL-1B-511T型增加，IL-1B-31C型增加。TNFα-308位点胃癌患者和健康对照组的基因型均以G型为主，基因型分布无明显差异（P〉0.05）。结论IL-1B-511位点T型或IL-1B-31位点C型会增加患胃癌的机率（OR=1．38），而TNFα-308基因型不会增加胃癌的发病风险。     

传递不平衡检测IL-1β基因多态性和IgA肾病的相关性

目的研究IL-1β基因多态性和IgA肾病及临床表现间的相关性。方法采用PCR-RFLP测定IL-1β-511、-31和＋3953SNP多态性。用TDT、sTDT、1-TDT及病例对照分析对位点和IgA肾病及临床表现的相关性进行分析。结果IL-1β-511T、-31C和＋3953C等位基因与IgA肾病具有相关性（P值分别为0.022,0.041和0.025）。伴大量蛋白尿的IgA肾病患者等位基因-511T和-31C的携带率较高。IL-1β基因的多态性和IgA肾病肉眼血尿、高血压及病理改变无相关性。结论IL-1β的基因多态性与IgA肾病及伴大量蛋白尿间有相关性。     

白细胞介素-1基因多态性及幽门螺杆菌感染与胃癌相关性研究

摘要：目的：研究白细胞介素(IL)-1B-31、IL-1B-511基因多态性在胃癌（GC）患者及体检健康者中的分布及幽门螺杆菌（Hp）感染情况,探讨其与GC易感性之间的关系。 方法：用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测128例GC患者和127例体检健康者IL-1B-31及511位点的基因多态性,用免疫印迹法检测GC组与健康对照组的Hp感染情况并分析各位点的基因型分布和等位基因频率。 结果：GC组及健康对照组符合Hardy-Weinberg 遗传平衡（P>0.05）。GC组IL-1B-31的基因频率（TT：15.63%、TC：51.65%、CC：32.81%）与健康对照组（TT：22.83%、TC：55.12%、CC：22.05%）相比,有显著性差异（χ²=4.57,P＜0.05）,GC组IL-1B-511-位点的基因频率（CC：21.88%、TC：47.66%、TT：30.47%）与健康对照组（CC：29.13%、TC：55.91%、TT：14.96%）相比也有显著性差异（χ²=8.90,P<0.01）。GC组IL-1B-31CC基因型频率［OR=2.13,95%CI (1.01~4.50）］和C等位基因型频率［OR=1.44,95%CI (1.01~2.04）］均高于健康对照组。〖STBX〗IL1B511〖STBZ〗TT基因型频率［OR=2.71,95%CI (1.30~5.67）］及T等位基因型频率［OR=1.58,95%CI (1.11~2.24）］均高于健康对照组。在Hp感染阳性的GC组IL-1B-31 CC基因型频率［OR=3.33,95%CI(1.15~9.63)］显著高于健康对照组,IL-1B-511 TT基因型频率［OR=5.75,95% CI (1.73~19.15)］亦显著高于健康对照组。 结论: IL-1B-31 CC及IL-1B-511 TT基因型增加GC的发病风险且与Hp感染对于GC的发生可能有协同作用。     

IL-1B基因-31位点基因多态性与胃癌的关系

目的研究白介素1B(interleukin-1B,IL-1B)基因启动子区-31位点基因多态性在正常人群和胃癌患者中的分布,分析IL-1B-31基因多态性分布是否与性别有关,探讨IL-1B-31基因多态性与胃癌发生的关系。方法收集101例胃癌患者和113名正常健康人外周血标本,提取DNA,用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测IL-1B启动子区-31位点基因多态性(C→T)。结果IL-1B基因-31位点基因多态性在正常人群和胃癌患者中的分布无显著性差异,与性别无关,携带-31C等位基因可增加患胃癌的危险性。结论IL-1B-31位点基因多态性可能与胃癌的发生无关。     

慢性乙型肝炎患者白细胞介素1β及白细胞介素1受体拮抗剂基因多态性分析

目的探讨白细胞介素1β(IL-1β)基因启动子区域-511C/T和白细胞介素1受体拮抗剂(IL-1RN)基因在慢性乙型肝炎及正常人群中的多态性,初步分析其基因型与慢性乙型肝炎的相关性.方法对190例慢性乙型肝炎患者和249例正常人IL-1β、IL-1RN基因进行PCR扩增,其中IL-1β基因用AvaI限制性内切酶对PCR产物进行消化,然后经琼脂糖凝胶电泳分别对IL-1β、IL-1 RN基因多态性进行分析.结果慢性乙型肝炎患者IL-1RN 1/2基因型和IL-1RN2等位基因频率均明显低于正常对照组(P<0.025,P<0.05).在乙型肝炎病毒(HBV) DNA水平不同的2组慢性乙型肝炎患者中,IL-1β基因启动子-511位点CC型分布差异有显著性(χ2=4.77,P<0.05).结论慢性乙型肝炎与IL-1β、IL-1RN基因的多态性有关,其中IL-1RN2等位基因可能对乙型肝炎病毒感染有保护作用,而IL-1β基因中的CC型可能对感染后HBV DNA的复制有抑制作用.     

幽门螺杆菌感染患儿血浆及胃黏膜 IL-6水平分析

目的：检测幽门螺杆菌（H．pylori）感染患儿血浆及胃黏膜白细胞介素-6（IL-6）的水平,探讨其与 H．pylori 感染的关系。方法采用酶联免疫吸附法（ELISA 法）,检测96例儿童血浆及胃黏膜 IL-6水平,其中 H ．pylori 感染患儿52例,非 H ． pylori 感染患儿44例。结果血浆 IL-6在 H ．pylori 感染组和非 H ．pylori 感染组的浓度分别是（173．36±143．15）pg/mL 和（168．55±99．67）pg/mL,两组比较差异无统计学意义（P ＞0．05）。胃黏膜 IL-6在 H ．pylori 感染组和非 H ．pylori 感染组的浓度分别是（210．54±53．68）pg/mL 和（140．59±73．43）pg/mL,两组比较差异有统计学意义（P ＜0．05）。幽门螺旋杆菌感染程度越严重,胃黏膜组织中 IL-6水平就越高,两者呈正相关（R 2＝0．868）。结论H ．pylori 感染患儿的血浆 IL-6水平不升高,但胃黏膜的 IL-6水平升高,其升高水平与感染程度相关,IL-6可能参与了 H ．pylori 感染的病理损伤过程,值得临床重视。     

Toll样受体10基因启动子区rs10004195基因多态性与幽门螺杆菌感染的相关性分析

目的探讨Toll样受体10(TLR-10)基因启动子区rs10004195基因多态性与幽门螺杆菌(H.pylori)感染的相关性。方法选取13C-尿素呼气试验确诊的H.pylori阳性201例与阴性182例,用测序方法检测TLR10启动子区rs10004195基因型。结果病例rs10004195基因型分布符合Hardy-Weinberg平衡(P0.05)。H.pylori阳性组AA基因型频率(26.9%)明显高于H.pylori阴性组(18.1%)(χ2=4.150,P0.05,OR=1.66,95%CI:1.02~2.71)。结论 TLR10启动子区rs10004195基因多态性与H.pylori的易感性有关,AA基因型者易感染H.pylori。     

幽门螺旋杆菌感染与上消化道症状的相关性研究

目的 分析幽门螺旋杆菌(H.pylori)感染与不同上消化道症状出现的相关性.方法 199例患者的胃黏膜标本用来做本次研究,使用Real-time PCR检测H.pylori的保守基因ure以判断H.pylori的感染.结果 199例患者中,H.pylori 阳性121例(60.8%),有反酸嗳气症状者65例(32.7%),恶心呕吐者8例(4%),食欲不振者65例(32.7%),慢性腹痛者89例(44.7%).H.pylori感染与反酸嗳气(χ2=0.22;P=0.64)、恶心呕吐(χ2=0.01;P=0.92)及食欲不振(χ2=1.92; P=0.17)无显著相关性,但H.pylori阳性人群中出现慢性腹痛症状者明显多于H.pylori阴性的人群(χ2=8.33; P=0.004).结论 H.pylori 可能在慢性腹痛症状的出现过程中发挥着潜在的作用.     

广州地区消化道疾病患者中H.pylori ureA和vacA s1基因及cagA基因亚型分布

目的 分析研究广州地区消化道疾病患者中H.pylori ureA、vacA s1基因和cagA基因亚型(ABC、ABD、ABAB、AAD等)的分布状况及其与胃黏膜病理检测结果间的相关性.方法 随机选取227例消化道疾病患者的胃黏膜标本,分别来自病理组织学检测无病理改变者46例,慢性胃炎130例,消化性溃疡29例,萎缩性胃炎15例,胃癌7例.并用实时荧光定量PCR检测H.pylori ureA基因、vacA s1基因,用PCR扩增cagA羧基端EPIYA基序所在区,然后测序确定其亚型.以保守基因ureA的存在判断H.pylori感染.结果 227例消化道疾病患者中,有50.7% (115/227)的患者H.pylori阳性,其中,vacA s1基因阳性91.3%(105/115),cagA基因阳性78.3%(90/115).4种cagA-EPIYA亚型分布为,ABC 17.8%(16/90)、ABD 78.9%(71/90)、AAD 2.2%(2/90)、ABAB 1.1%(1/90).无病理改变组中H.pylori 阳性32.6%(15/46),vacA s1基因阳性28.3%(13/46),cagA基因阳性26.1%(12/46);慢性胃炎组H.pylori 阳性48.5%(63/130),vacA s1基因阳性43.8%(57/130),cagA基因阳性36.2%(47/130);溃疡组H.pylori 阳性72.4%(21/29),vacA s1基因阳性65.5%(19/29),cagA基因阳性55.2%(16/29);萎缩性胃炎组H.pylori 阳性66.7%(10/15),vacA s1基因阳性66.7%(10/15),cagA基因阳性66.7%(10/15);胃癌组H.pylori阳性85.7%(6/7),vacA s1基因阳性85.7%(6/7),cagA基因阳性71.4%(5/7).H.pylori在不同胃黏膜病理组的分布差异有统计学意义(χ2=16.72;P<0.01),溃疡、萎缩性胃炎、胃癌组中H.pylori的分布明显高于无病理改变与炎症组(χ2=16.02;P<0.01).但在H.pylori阳性患者中,强毒力因子vacA s1基因(χ2=2.00;P=0.74)、cagA基因(χ2=3.44;P=0.49)及cagA-EPIYA亚型(χ2=3.66;P=0.45)在无病理改变、炎症、溃疡、萎缩性胃炎及胃癌组中的分布差异均无统计学意义.结论 广州消化道疾病患者中H.pylori的感染与胃黏膜病理改变显著相关,而广州地区消化道疾病患者中H.pylori高毒力亚型的强致病性并不明显,需扩大标本量,再细化疾病种类进一步分析高毒力H.pylori对胃肠道疾病发生的影响.

Abstract：

Objective To detect the distribution of H.pylori ureA, vacA s1 gene and cagA subtype(ABC, ABD, ABAB, AAD, et al) in patients with digestive diseases in Guangzhou and investigate the relationship with the pathological findings of gastric mucosa.Methods A total of 227 randomly selected gastric mucosa from patients with digestive diseases were enrolled in the research, including 46 without pathological changes, 130 with chronic gastritis, 29 with peptic ulcer, 15 with atrophic gastritis and 7 with gastric cancer.Real-time PCR assay were used to detect Helicobacter pylori ureA gene and vacA s1 gene.EPIYA motifs in the 3′ region of cagA were amplified by conventional PCR followed by subtype sequencing. The conserved gene ureA was used to detect H.pylori infection.Results Among the 227 patients with digestive diseases, 50.7% (115/227) patients were H.pylori positive, in which 91.3%(105/115) carried vacA s1 and 78.3% (90/115) carried cagA. Four types of cagA-EPIYA subtype were detected, including ABC 17.8%(16/90), ABD 78.9%(71/90), AAD 2.2%(2/90) and ABAB 1.1%(1/90).In the non-pathological change group, 32.6% (15/46) were H.pylori positive, in which 28.3% (13/46) carried vacA s1 and 26.1% (12/46) carried cagA;in chronic gastritis group, it was 48.5% (63/130), 43.8% (57/130) and 36.2% (47/130), respectively;in ulcer group, it was 72.4% (21/29), 65.5% (19/29) and 55.2% (16/29), respectively;in atrophic gastritis group, it was 66.7% (10/15), 66.7% (10/15) and 66.7% (10/15), respectively;in gastric cancer group, it was 85.7% (6/7), 85.7% (6/7) and 71.4% (5/7), respectively.The distribution of H.pylori among the 4 groups had statistical significance (χ2=16.72;P<0.01). H.pylori was more prevalent in ulcer, atrophic gastritis and cancer group than in inflammation group and non-pathological change group (χ2=16.02;P<0.01).In patients infected by H.pylori, there was no significant difference in the distribution of vacA s1 gene as high virulence factors among non-pathological change, inflammation, ulcer, atrophic gastritis and cancer group (χ2=2.00;P=0.74), as well as cagA (χ2=3.44;P=0.49) and EPIYA subtypes (χ2=3.66;P=0.45).Conclusions H.pylori infection is significantly associated with the pathological change of gastric mucosa for patients with digestive diseases in Guangzhou, while the relationship with the pathogenicity of H.pylori with high virulence genotype is not significant.More samples and diseases reclassification are needed to make an advanced analysis of the effect of H.pylori with high virulence in gastrointestinal diseases development.     

Association of interleukin-1 genetic polymorphisms with the risk of rheumatoid arthritis in Chinese population.

BACKGROUND: Previous studies suggest that a variable number of tandem repeats polymorphism in the second intron of the interleukin-1 receptor antagonist gene and two single nucleotide polymorphisms at positions -511 and +3954 of the interleukin-1beta (IL-1B) gene are associated with an increased risk of autoimmune diseases. In the present study, we evaluated associations between these genetic factors and an increased risk of rheumatoid arthritis (RA) in a population from Northwest China. METHODS: A total of 240 patients with RA and 227 healthy controls from Northwest China were investigated using PCR and PCR-restriction fragment length polymorphism. Genotype and allele distributions and haplotype construction were analyzed. RESULTS: The genotype and allele distributions of IL-1B +3954 and IL-1RN polymorphisms were significantly different in RA patients compared to controls (p<0.001 and p<0.001; p=0.028, p=0.023, respectively). Significant differences were also observed between the RA and control groups for the haplotypes IL-1B -511C/+3954C/IL-1RN *1, IL-1B -511C/+3954T/IL-1RN *1 and IL-1B -511T/+3954T/IL-1RN *1 [p=0.017, odds ratio (OR) 0.721, 95% confidence interval (CI) 0.551-0.944; p=0.030, OR 2.111, 95% CI 1.060-4.204; and p=0.029, OR 2.909, 95% CI 1.066-7.902, respectively]. CONCLUSIONS: These findings suggest that IL-1B +3954 and IL-1RN genetic polymorphisms are associated with a significantly increased risk of RA in this Chinese population.     

PCR-monitoring of gastric juice obtained with the capsuled string for the evaluation of H. pylori eradication

We have developed a highly sensitive semi-nested PCR assay, URA-PCR, for the detection of H. pylori ureA gene in gastric juice. The primers were designed according to nucleotide sequence analyses of clinical isolates. The PCR assay has higher sensitivity than conventional methods such as culture. Characteristics of culture-negative but PCR-positive patients were similar to those of culture-positive ones. The PCR assay, using gastric juice samples obtained with capsuled strings, detected 97% cases of relapsed infection within eight weeks after antimicrobial therapy.     

Genetic association of interleukin-1beta (-511C/T) and interleukin-1 receptor antagonist (86 bp repeat) polymorphisms with Type 2 diabetes mellitus in North Indians

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with a subclinical systemic inflammation and development of complications like nephropathy, retinopathy, neuropathy and hypertension. We studied the genetic association of bi-allelic polymorphism (-511C/T) of interleukin (IL)-1beta and 86 bp variable number tandem repeat (VNTR) polymorphism of natural receptor antagonist (IL-1RN) with T2DM and associated complications in North Indians. METHODS: We genotyped 200 patients with T2DM and 223 healthy control subjects for IL-1beta (-511C/T) by PCR-RFLP. Genotyping of IL-1RN (VNTR) polymorphism was determined by gel electrophoresis after PCR amplification. RESULTS: Interleukin-1beta (-511C/T) and IL-1RN (VNTR) polymorphisms were significantly associated with T2DM. IL-1beta -511T, IL-1RN*2 and IL-1RN*3 alleles were associated with high risk of T2DM whereas; individuals with IL-1beta -511C and IL-1RN*1 alleles were at low risk. Haplotype frequency analysis showed that T2 (IL-1beta -511T/IL-1RN*2) haplotype was associated with the high risk (p=0.000; OR=2.4, 95% CI 1.68-3.34) and C1 (IL-1beta -511C/IL-1RN*1) haplotype showed low risk (p=0.000; OR=0.38, 95% CI 0.27-0.53). Further, CT, TT genotypes of IL-1beta (-511C/T) and 1/2 genotype of IL-1RN (VNTR) were found to be associated with risk of complications particularly with nephropathy in T2DM. CONCLUSION: The IL-1beta (-511C/T) and IL-1RN (VNTR) polymorphisms are significantly associated with increased risk of T2DM as well as associated complications in North Indians.     

Influences of proinflammatory and anti-inflammatory cytokine polymorphisms on eradication rates of clarithromycin-sensitive strains of Helicobacter pylori by triple therapy

BACKGROUNDS AND AIMS: Polymorphisms of proinflammatory cytokines, such as interleukin (IL) 1beta and tumor necrosis factor (TNF) alpha, are associated with individual differences in gastric mucosal inflammation and acid inhibition in response to Helicobacter pylori infection. We investigated whether inflammation-related cytokine polymorphisms would influence the eradication rates of H pylori by a triple-therapy regimen. METHODS: Three hundred sixty patients infected with clarithromycin-sensitive strains of H pylori were genotyped for IL1B -511, IL1RN, TNFA -857/-863/-1,031, IL10 -1,082/-819/-592, and CYP2C19 and underwent triple therapy for 1 week with a proton pump inhibitor (20 mg omeprazole, 30 mg lansoprazole, or 10 mg rabeprazole) twice daily, 400 mg clarithromycin twice daily, and 750 mg amoxicillin (INN, amoxicilline) twice daily. The influences of the previously mentioned polymorphisms on the eradication rates were analyzed. RESULTS: The intention-to-treat-based total eradication rate was 83.6% (301/360). The logistic regression analysis revealed that polymorphisms of CYP2C19 and IL1B -511 were independently associated with the eradication rates, but other cytokine polymorphisms were not associated with these rates. The eradication rates in patients with IL1B -511 C/C, C/T, and T/T genotypes were 72.2% (70/97), 87.7% (164/187), and 88.2% (67/76), respectively (P = .0017). When patients were stratified by CYP2C19 genotype status, IL1B -511 genotype-dependent differences in eradication rates were observed in homozygous extensive metabolizers (EMs) but not in heterozygous EMs and poor metabolizers of CYP2C19. The eradication rate in homozygous EM patients with the IL1B -511 C/C genotype was quite low (51.1% [22/43]). CONCLUSIONS: IL1B -511 polymorphism, but not IL1RN, TNFA, or IL10 polymorphism, is one of the determinants of triple therapy for clarithromycin-sensitive strains of H pylori in CYP2C19 homozygous EMs.     

Sex influences on the penetrance of IL-1beta and IL-1RN genotypes for rheumatoid arthritis in the Chinese population

Polymorphism (variable number of tandem repeats) in the second intron of the interleukin-1 receptor antagonist (IL-1Ra) gene and two single nucleotide polymorphisms at positions -511 and +3954 of the IL-1beta gene may be associated with an increased risk of rheumatoid arthritis (RA). This study used sex stratification to investigate a correlation of the three genetic polymorphisms with the risk of RA, on patients with RA and healthy controls. Polymerase chain reaction (PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were performed. The frequencies of the IL-1beta+3954 allele and genotype in female patients were significantly different compared with the controls; but in males, only the frequency of the IL-1beta+3954 allele was different. The frequency of the IL-1RN genotype in patients was not statistically different compared with the controls; however, the frequency of IL-1RN allele in female patients was different. The association of the three polymorphisms with the susceptibility to RA appears to be significantly affected by gender.     

H. pylori infection: bacterial virulence factors and cytokine gene polymorphisms as determinants of infection outcome

The gram negative bacterium H. pylori infects the human stomach worldwide, invariably causing mucosal inflammation. In the majority of cases, H. pylori-associated gastritis remains the only clinical manifestation of the infection, which might cause, otherwise, peptic ulcer, gastric adenocarcinoma. or MALToma. The balance between the bacterial virulence machinery and the host response to the infection determines the different clinical outcomes. The main bacterial virulence factors comprise adhesins (BabA, SabA), the vacuolating cytotoxin VacA, and the products of cag pathogenicity island. The pattern of cytokine production in response to the infection is one of the main host determinants involved in limiting the infection outcome to gastritis or in favoring peptic ulcer or cancer onset. The polymorphisms of some cytokine genes (IL-1beta IL-1RN, TNF-alpha, IFN-gamma) have been correlated with H. pylori-associated gastric adenocarcinoma or peptic ulcer, possibly because they influence the amount of cytokine production in response to H. pylori infection. This review focuses on the role of H. pylori virulence genes and on host cytokines' genes polymorphisms in determining clinical outcome to H. pylori infection.     

Interleukin 1 beta and tumor necrosis factor levels in stored platelet concentrates and the association with gene polymorphisms

BACKGROUND: Cytokines (IL-1beta and TNF) generated by WBCs during storage of PLT concentrates have been associated with febrile nonhemolytic transfusion reactions. STUDY DESIGN AND METHODS: This study was undertaken to investigate whether there is an association between the polymorphisms of IL1B -511C/T and +3953C/T, IL1RN intron 2 VNTR and TNFA-308G/A genes and the increase of cytokines during the storage of PLT concentrates produced by plasma-rich PLTS (PRP-PC) or apheresis PLTs. RESULTS: Thirty PRP-PCs were studied and a progressive increase of IL-1beta and TNF during storage was revealed. IL1-beta and TNF levels were inversely correlated with the content of PLTs in PRP-PCs detected on Day 3 (p = 0.004) and Day 5 (p = 0.019), but not on Day 7. There was association of IL1B-511T polymorphism and IL-1beta levels (Day 5, p = 0.063, only tendency and on Day 7, p = 0.038, significant). There was no association of the other polymorphisms (IL1B+3953C/T, IL1RN intron 2 and TNFA-308G/A) with their respective cytokines. CONCLUSION: The great variation of cytokine levels in the plasma of PLT concentrates (PCs) during storage may also be caused by cytokine gene polymorphisms, as well as WBC contamination, material that the bags are made of, and storage time, as previously described.     

Extremely high interleukin-6 blood levels and outcome in the critically ill are associated with tumor necrosis factor- and interleukin-1-related gene polymorphisms

OBJECTIVE: To determine the allelic frequencies of interleukin (IL)-6-, IL-1-, and tumor necrosis factor-alpha (TNF)-related gene polymorphisms in critically ill patients with extremely high IL-6 blood level and to examine the genetic effects on their clinical courses. DESIGN: Population-based association study. SETTING: A general intensive care unit in a university teaching hospital. PATIENTS: A total of 150 consecutive critically ill patients recruited at admission to the intensive care unit, regardless of diagnosis, and 150 healthy volunteers. MEASUREMENTS AND MAIN RESULTS: IL-6 blood levels were measured daily with chemiluminescence immunoassay. The IL-6 peak levels were significantly correlated with simultaneously measured TNF (r = .659, p < .0001) and IL-1beta levels (r = .518, p < .0001), respectively. Single nucleotide polymorphism at position -174 and -596 sites of the IL-6 (IL6-174*G/C and IL6-596*G/A), -308 site of the TNF (TNF-308*G/A), and -511 site of the IL-1beta (IL1B-511*C/T) were identified with real-time polymerase chain reaction assay using specific fluorescence-labeled probe. Within the IL-1 receptor antagonist intron 2, a various number of tandem repeat polymorphisms (IL1RN*1-5) were identified after polymerase chain reaction with gel electrophoresis. Allelic frequencies of patients with IL-6 peak levels of > or =10,000 pg/mL (group A) were compared with those of patients with IL-6 peak levels of <10,000 pg/mL (group B). Neither IL6-174*C nor IL6-596*A were recognized in all the subjects; however, group A showed a higher frequency of TNF-308*A (p = .054), IL1B-511*T (p = .013), and non-IL1RN*1 (p = .008) allele compared with group B. TNF-308*A, IL1RN*2 or IL1RN*3 allele carriers of group A showed sustained high IL-6 levels, despite countermeasures against hypercytokinemia, and their survival rate was lower than that of the noncarriers of those high-risk alleles (p = .025). CONCLUSIONS: TNF-308*A, IL1RN*2, and IL1RN*3 alleles were associated with the prevalence of the extremely high IL-6 blood level in the critically ill, their uncontrollable blood IL-6 kinetics, and outcome.