PURPOSE: Interleukin-1 (IL-1) plays a key role in inflammation and immunity and its decoy receptor, IL-1R2, has been implicated in transcriptomic and genetic studies of asthma. METHODS: Two large asthma family collections, the French-Canadian Saguenay-Lac-St-Jean (SLSJ) study and the French Epidemiological Study on the Genetics and Environment of Asthma (EGEA), were used to investigate the association of SNPs in 10 genes that modulate IL-1R2 activities with asthma, allergic asthma, and atopy. Gene-gene interactions were also tested. RESULTS: One SNP in BACE2 was associated with allergic asthma in the SLSJ study and replicated in the EGEA study before statistical correction for multiple testing. Additionally, two SNPs in the MMP2 gene were replicated in both studies prior to statistical correction and reached significance in the combined analysis. Moreover, three gene-gene interactions also survived statistical correction in the combined analyses (BACE1-IL1RAP in asthma and allergic asthma and IL1R1-IL1RAP in atopy). CONCLUSIONS: Our results highlight the relevance of genes involved in the IL-1R2 activity in the context of asthma and asthma-related traits.
Asthma ; Epidemiologic Studies ; Genetics ; Humans ; Inflammation ; Interleukin-1* ; Phenotype* ; Polymorphism, Single Nucleotide ; Receptors, Interleukin-1 Type II*

OBJECTIVETo investigate the correlation between the polymorphisms of apolipoprotein E(APOE), the interleukin-1 alpha (IL-1 alpha ) genes and the susceptibility to Alzheimer's disease(AD).

METHODSAssociation study was performed in 114 AD patients and 113 healthy elderly individuals from Chengdu, China. Polymorphisms of APOE and IL-1 alpha genes were analyzed with polymerase chain reaction-restriction fragment length polymorphism.

RESULTSThe frequency of APOE-epsilon 4-carrying genotype in moderate to severe AD patients (28.6%) was higher than that of mild patients (18.5%) and the controls (14.2%), and the difference between moderate to severe AD group and the control group was significant (OR=2.4, 95%CI: 1.1-5.5). The frequency of epsilon 4 was also of significant difference between the group of moderate to severe dementia and the control group (OR=2.6, 95%CI: 1.3-5.3). However, no significant difference in distribution of IL-1 alpha polymorphism between AD patients and controls was observed.

CONCLUSIONThe APOE epsilon 4 allele was associated with moderate to severe AD while no association between the IL-1 alpha gene polymorphism and AD was found.

Alzheimer Disease ; genetics ; Apolipoproteins E ; genetics ; Humans ; Interleukin-1 ; genetics ; Polymorphism, Genetic

OBJECTIVETo determine the relationship between polymorphisms in the genes encoding IL-1, IL-6, and IL-10 with primary biliary cirrhosis (PBC) in Chinese population.

METHODSWhole-blood samples were taken from 77 patients with PBC and 160 healthy controls. DNA was extracted and the polymorphisms at positions IL-1 +3953, IL-1RN intron 2, IL-6 -174, and IL-10 -1082, -819, and -592 were determined by using sequence-specific polymerase chain reaction (SSP) or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

RESULTSThe frequency of IL-1RN1,1 allele in PBC group was significantly higher than in control group (90.9% vs 79.4%, P=0.026), and the frequency of IL-1RN1,2 in PBC group was significantly lower than in control group (6.5% vs 18.8%, P=0.013). There was no significant difference in the frequence of IL-1RN*2 allele between PBC group and control group (P=0.06). Of the 77 patients with PBC, 4 patients were IL-6 -174GC, 73 were IL-6 174GG. All the 160 health controls are IL-6 -174GG (P=0.0036). The frequence of IL-6 -174C allele in PBC group was significantly higher than that in control group (P=0.0038). No significant differences of polymorphisms for IL-1 +3953 and IL-10 (-1082, -819 and -592) were found between PBC group and control group.

CONCLUSIONThe polymorphisms of IL-1RN and IL-6 -174G/C appear to be associated with PBC, and the polymorphisms of IL-1 +3953 and IL-10 promoter gene are not associated with PBC in a Chinese population.

Adult ; Aged ; Female ; Humans ; Interleukin-1 ; genetics ; Interleukin-10 ; genetics ; Interleukin-6 ; genetics ; Liver Cirrhosis, Biliary ; genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; methods ; Polymorphism, Restriction Fragment Length

OBJECTIVEThe expressions of caspase-1 and cytokines activated by caspase-1 are associated with the pathophysiology of many diseases for its proinflammatory and proapototic peculiarity. However its relationship to brain injury of developing rats following recurrent seizures has not yet been identified. This study aimed to investigate the role of caspase-1 and cytokines activated by caspase-1 in brain injury of developing rats following recurrent seizures.

METHODSA total of 96 postnatal 20 day Sprague-Dawley rats were randomly assigned into Control and Seizure groups. Seizures were induced in the Seizure group by flurothyl inhalation daily for six days. Brain tissues were sampled at 6 hrs, and at 1, 3, and 7 days after last seizure. The expressions of caspase-1, interleukin (IL)-18 and IL-1beta mRNA in the cerebral cortex were detected by RT-PCR. The water content of the brain and the pathological changes of cortex nerve cells were observed. Brain injury was evaluated using a semiquantitative neuropathological scoring system.

RESULTSThe levels of caspase-1 and IL-18 mRNA in the cerebral cortex of the Seizure group were obviously higher than those in the Control group at 6 hrs, and at 1, 3, and 7 days after seizure (P < 0.05 or P < 0.01). The expression of IL-1beta mRNA in the Seizure group exhibited a biphasic pattern: increased significantly at 6 hrs, and at 1 and 7 days post-seizure (P < 0.01), but was not significantly different from the Control group at 3 days post-seizure. Edema, degeneration and necrosis of nerve cells in cerebral cortex, accompanying by inflammatory cell infiltration and apoptosis of nerve cells, were observed under a light microscope in the Seizure group after recurrent seizures. The water content of the brain in the Seizure group increased significantly compared with that in the Control group at 6 hrs, and at 1 and 3 days after recurrent seizures (P < 0.01). The Seizure group had significantly higher neuropathological scores than the Control group at each time point (P < 0.01).

CONCLUSIONSCaspase-1 and cytokines activated by caspase-1 play an important role in the developing brain injury after recurrent seizures.

Animals ; Brain ; pathology ; Caspase 1 ; genetics ; physiology ; Female ; Interleukin-1 ; genetics ; physiology ; Interleukin-18 ; genetics ; physiology ; Male ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Recurrence ; Seizures ; pathology

OBJECTIVETo investigate the polymorphisms of interleukin-1B (IL-1B) promoter region -511C/T and interleukin-1 receptor antagonist (RN) gene, the relationship between the genotype of IL-1B and IL-1RN, and the susceptibility to chronic hepatitis B in Chinese population.

METHODSGenomic DNA was extracted from the peripheral blood of 190 patients with chronic hepatitis B and 249 normal controls and then was subjected to PCR amplification. The PCR product was digested by restriction endonuclease Ava I. The product of digestion was subjected to 2% gel-electrophoresis and ethidium bromide staining.

RESULTSThe IL-1B -511C allele was detected in 0.50 of normal controls and 0.48 of patients, while the IL-1B -511T allele was detected in 0.50 of normal controls and 0.52 of patients. The frequency of CC genotype was 0.26 (65/249) and in normal controls 0.24 (45/190) in patients. The frequency of CT genotype was 0.47 (118/249) in normal controls and 0.49 (94/190) in patients. The frequency of TT genotype was 0.27 (66/249) in normal controls and 0.27 (51/190) in patients. The HBV-DNA copies in chronic hepatitis B with CC genotype were significantly decreased, compared with controls (P<0.05). Only four (1/1, 1/2, 2/2 and 1/4) of the five kinds of polymorphism of IL-1RN were found in this study. The frequencies of 1/1, 1/2, 2/2 and 1/4 were 0.88, 0.09, 0.01 and 0.02 in chronic hepatitis B patients respectively, while in controls were 0.81, 0.16, 0.01 and 0.02. The IL-1 RN*1 allele was detected in 0.94 of chronic hepatitis B patients and in 0.90 of controls, while the IL-1RN*2 allele was detected in 0.05 of patients and in 0.09 of normal controls. The frequencies of 1/2 genotype and IL-1RN*2 allele were lower in chronic hepatitis B than in controls (P<0.05).

CONCLUSIONThe polymorphisms of the promoter region -511C/T of IL-1B gene and IL-1RN intron 2 gene are associated with the development of chronic hepatitis B. The people with IL-1RN*2 allele may be protected against HBV infection, and the IL-1B -511 CC genotype may be linked to HBV-DNA copy.

Adolescent ; Adult ; Aged ; Child ; Female ; Genotype ; Hepatitis B, Chronic ; genetics ; Humans ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-1 ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Sialoglycoproteins ; genetics

Osteoarthritis is a common joint disease, which seriously affects the patient's health and quality of life. It results in substantial social and economic costs. Etiology and pathogenesis of OA is still not completely clear, but people paid more attention on Cytokines, especially IL-1, which is considered as core factor in the development of OA. In recent years, many clinical trials considered IL-1 as a target treatment for OA. It provided a new treatment method. This article is to overview the mechanism of IL-1 in OA cartilage damage.
Animals ; Disease Progression ; Humans ; Interleukin-1 ; genetics ; immunology ; Osteoarthritis ; genetics ; immunology ; pathology

OBJECTIVE: To observe the effects of herbal cake separated moxibustion on macrophage effector molecule T-cell immunoglobulin and mucin-domain containing-4 (Tim-4) and ubiquitination of programmed cell death protein 1 (PD-1) in rabbits with immunosuppression, and to explore the possible mechanism on herbal cake separated moxibustion in improving immunosuppression. METHODS: Thirty-two big-ear white rabbits were randomly divided into a normal group, a model group, a moxa stick moxibustion group and a herbal cake separated moxibustion group, 8 rabbits in each group. Except the normal group, the immunosuppression model was established by intraperitoneal injection of cyclophosphamide of60 mg/kg in the other 3 groups. "Shenque" (CV 8), "Shenshu" (BL 23), "Zusanli" (ST 36), etc. were selected in both the moxa stick moxibustion group and the herbal cake separated moxibustion group. Moxa stick moxibustion was applied in the moxa stick moxibustion group, one cone at each acupoint; herbal cake separated moxibustion was applied in the herbal cake separated moxibustion group, 5 cones at each acupoint. The intervention was given once every other day for 10 times in both groups. Leukocyte content in peripheral blood was detected by blood cell analyzer; the positive expression of PD-1 in CD⁺₄ T lymphocytes, CD⁺₈T lymphocytes and CD⁺₆₈ macrophages in peripheral blood was measured by flow cytometry, the serum levels of interleukin 2 (IL-2), CD₈, CD₆₈ and Tim-4 were detected by ELISA, and the expression of Tim-4 and F-box only protein 38 (FBXO38) in the liver and spleen tissues was measured by immunohistochemistry. RESULTS: Compared with the normal group, in the model group, white blood cell count (WBC) and percentage of neutrophils (NEU%) were decreased while percentage of lymphocyte (LYM%) was increased (P<0.01) in peripheral blood; the positive expression rates of PD-1 in CD⁺₄ T lymphocytes, CD⁺₈T lymphocytes and CD⁺₆₈ macrophages in peripheral blood were increased (P<0.01); the serum levels of IL-2, CD₆₈ and Tim-4 were increased (P<0.01), the serum level of CD₈ was decreased (P<0.01); the average optical density (AOD) of Tim-4 in the liver tissue and FBXO38 in the liver and spleen tissues was increased (P<0.01). Compared with the model group, in the moxa stick moxibustion group and the herbal cake separated moxibustion group, WBC and NEU% were increased (P<0.01); the positive expression rates of PD-1 in CD⁺₄ T lymphocytes, CD⁺₈T lymphocytes and CD⁺₆₈ macrophages in peripheral blood were decreased (P<0.01); the serum levels of IL-2, CD₆₈ and Tim-4 were decreased (P<0.01), the serum levels of CD₈ were increased (P<0.01); the AOD of Tim-4 and FBXO38 in the liver tissue and FBXO38 in the spleen tissue was decreased (P<0.01, P<0.05). Compared with the moxa stick moxibustion group, in the herbal cake separated moxibustion group, the positive expression rate of PD-1 in CD⁺₆₈ macrophages in peripheral blood was increased (P<0.05); serum level of Tim-4 was increased (P<0.01); AOD of Tim-4 in the liver tissue was decreased (P<0.05). CONCLUSION Herbal cake separated moxibustion can improve immunosuppression by regulating the expression of macrophage effector molecule Tim-4 and the FBXO38 mediated ubiquitination of PD-1, Tim-4 may be one of the specific indexes of immunomodulation involving with herbal cake separated moxibustion.
Animals ; Rabbits ; Interleukin-2/genetics* ; Moxibustion ; Programmed Cell Death 1 Receptor/genetics* ; Immunosuppression Therapy ; Ubiquitination

To investigate the function of B7 co-stimulator in activation and differentiation of T cell, B7 gene was transfected into Raji and Jurkat cells by liposome, B7 expression in tumor cells was detected with flow cytometry, and expression of IL-2, IL-4 and IFN-gammamRNA was detected by RT-PCR. Kinetics of secretion of three cytokines was also analyzed at 4, 12, 20 and 48 hours after gene transfection. The results showed that B7(+) Raji cells could induce mRNA expression of IL-2, IL-4 and IFN-gamma on T cell surface; B7(+) Jurkat cells could induce secretion of IL-2 and IFN-gamma. However, B7(-) Raji and B7(-) Jurkat cells could not induce secretion of cytokines. Kinetics of the three cytokines secretion were different, IL-2 and IL-4 were only detectable after 4 hours of T cell activation, whereas IFN-c was detectable after 12 hours of stimulation. The peak levels of IL-2, IL-4 and IFN-gamma were found at 20 hours after activation. It was concluded that tumor cell lines transfected with B7 gene could enhance their immunocompetence, activating T cell efficiently and B7-1 play more critical role in T cell activation and differentiation.
B7-1 Antigen ; genetics ; physiology ; Cytokines ; genetics ; Humans ; Interferon-gamma ; genetics ; Interleukin-2 ; genetics ; Interleukin-4 ; genetics ; Jurkat Cells ; RNA, Messenger ; analysis ; Transfection

OBJECTIVETo investigate whether interleukin-1 beta (IL-1beta ) and interleukin-1 receptor antagonist (IL-1RA) gene polymorphisms are associated with endometriosis (EMs) in Chinese women.

METHODSOne 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).

RESULTThere 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).

CONCLUSIONAssociation 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.

Adult ; Alleles ; China ; Endometriosis ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Interleukin 1 Receptor Antagonist Protein ; genetics ; Interleukin-1beta ; genetics ; Polymorphism, Genetic

BACKGROUNDBacteremia remains a significant cause of morbidity and mortality after kidney transplantation. This study was conducted to investigate whether the polymorphisms of tumor necrosis factor (TNF)-β, interleukin (IL)-1β, and IL-1 receptor antagonist (IL-1ra) gene predicted the susceptibility to bacteremia within the first 6 months after kidney transplantation.

METHODSSubjects comprised 82 infected kidney transplant recipients and 60 non-infected kidney transplant recipients. Bacteremia was diagnosed in 16 of the 82 infected recipients. Genomic DNA from these 142 kidney transplant recipients was extracted from peripheral blood leukocytes. Regions containing the NcoI polymorphic site at position +252 of TNF-β gene and the AvaI polymorphic site at position -511 of IL-1β gene were amplified by polymerase chain reaction (PCR) and subsequently digested with NcoI and AvaI restriction enzymes, respectively. The polymorphic regions within intron 2 of IL-1ra gene containing variable numbers of a tandem repeat (VNTR) of 86 base pairs were amplified by PCR.

RESULTSGenotypic and allelic frequencies were similar between infected recipients and non-infected ones. Individual locus analysis showed that recipient TNF-β and IL-1ra gene polymorphisms were not associated with the presence of bacteremia (P = 0.684 and P = 0.567, respectively). However, genotype analysis revealed that recipient IL-1β-511CC genotype was strongly associated with susceptibility to develop bacteremia (P = 0.003). Recipient IL-1β-511CC genotype (odds ratio 5.242, 95% confidence intervals 1.645-16.706, P = 0.005) independently predicted the risk for bacteremia within the first 6 months after kidney transplantation.

CONCLUSIONSThese findings indicate a critical role of IL-1β gene polymorphisms in susceptibility to bacteremia after kidney transplantation, which may be useful to screen for patients at higher risk for post-transplant bacteremias. Thus, the identified individuals can benefit from preventive treatment and a less potent immunosuppressive regimen.

Adolescent ; Adult ; Bacteremia ; genetics ; Female ; Genotype ; Humans ; Interleukin 1 Receptor Antagonist Protein ; genetics ; Interleukin-1 ; genetics ; Kidney Transplantation ; Lymphotoxin-alpha ; genetics ; Male ; Middle Aged ; Multigene Family ; genetics ; Polymorphism, Genetic ; genetics ; Young Adult