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Biomedical subjects

M Hurme

Publications and source records attributed to M Hurme.

At least 55 records · Page 3Linked to original sources
PubMed2001

A study of interleukin-1 cluster genes in susceptibility to and severity of multiple sclerosis.

In this explorative study, interleukin-1 (IL-1) receptor antagonist (IL-1RA; polymorphism of variable number of tandem repeats: VNTR), IL-1alpha (-889), IL-1beta (-511) and IL-1beta (+3953) polymorphisms were studied in relation to susceptibility to and severity of multiple sclerosis (MS), in 93 MS patients and 400 normal controls. No associations were found for any polymorphisms, alone or in combination. However, in our MS cohort, females were found to be IL-1RA allele 2 carriers more frequently than males (33/49 vs. 16/44, p = 0.0028). Using a cohort of 109 controls, IL-1RA allele 2 carriers were more frequently women with MS than control women (33/49 vs. 23/43, odds ratio (OR) = 2.19, 95% confidence interval (CI) 1.02-4.72, p = 0.043, P(C) = ns). The data suggest that the IL-1 cluster genes make no major contribution to MS, but the tentative association between IL-1RA allele 2 and susceptibility of MS in women warrants further studies.

Adult↗
PubMed2001

Polymorphisms within the tumor necrosis factor locus and prevalence of coronary artery disease in middle-aged men.

Tumor necrosis factor (TNF) is an important cytokine in the inflammation process of atherosclerosis and is also involved in lipid metabolism. Two biallelic polymorphisms within TNF gene locus-TNFA at the position -308 in the promoter region of the TNF gene and TNFB in the first intron of the lymphotoxin-alpha (LT-alpha) have been reported to be associated with TNF production and with susceptibility to inflammatory diseases. We studied the association of these polymorphisms within the major histocompatibility complex (MHC) III region with coronary atherosclerosis and its manifestations. The autopsy series comprised 700 Caucasian Finnish men, aged 33-70 years (The Helsinki Sudden Death Study). Coronary stenosis and surface area of atherosclerotic changes (fatty streaks, fibrous plaques, complicated lesions and calcification) were measured and the presence of myocardial infarction and coronary thrombosis recorded. TNFA and TNFB genotypes were determined by the PCR-RFLP technique. The allele frequencies were TNFA1/TNFA2=0.88/0.12 and TNFB1/TNFB2=0.30/0.70. There was a strong linkage disequilibrium between the two polymorphisms. There were no differences in coronary stenosis and in the frequency of old or recent myocardial infarction or coronary thrombosis between men with different genotype status in either locus. Men with TNFA22 or TNFB11 genotype tended to have more fibrous lesions and calcification in their coronary arteries. TNFA and TNFB polymorphisms are unlikely to contribute to progression of atherosclerosis in a way clinically important.

Adult↗
PubMed2001

Genetic association between interleukin-10 promoter region polymorphisms and primary Sjögren's syndrome.

OBJECTIVE: To determine whether the haplotypes formed on the basis of single-base-exchange polymorphisms at positions -1082, -819, or -592 of the interleukin-10 (IL-10) gene predispose subjects to primary Sjögren's syndrome (SS). METHODS: The frequency of IL-10 polymorphisms was analyzed in 62 patients with primary SS and in 400 healthy subjects. These data were assessed for correlations with the concentration of IL-10 in the plasma. RESULTS: The frequency of the IL-10 GCC haplotype (G at position -1082, C at position -819, and C at position -592 of the IL-10 gene) was increased (P < 0.05, odds ratio [OR] 1.90, 95% confidence interval [95% CI] 0.955-3.62) and the frequency of the ACC haplotype decreased (P < 0.05, OR 0.443, 95% CI 0.257-0.764) in primary SS patients compared with healthy controls. Moreover, the frequency of the ATA haplotype was similar in primary SS patients and healthy controls, but the incidence of the GCC/ATA genotype was elevated in the primary SS patients (P < 0.05, OR 2.19, 95% CI 1.19-4.03). The concentration of plasma IL-10 was significantly higher in patients carrying the GCC haplotype than in non-carriers of GCC. CONCLUSION: These results suggest that the presence of the GCC haplotype or the GCC/ATA genotype and the absence of the ACC haplotype of the IL-10 gene are associated with an increased susceptibility to primary SS. This effect is probably mediated by the increased capability to produce IL-10 among carriers of the GCC haplotype.

Adolescent↗
PubMed2001

Lack of association between human longevity and polymorphisms of IL-1 cluster, IL-6, IL-10 and TNF-alpha genes in Finnish nonagenarians.

There has been increasing interest in research on genetic basis of longevity. Aging is accompanied by immune deterioration and dysregulation of cytokines. Increased IL-6 concentration in vivo and enhanced IL-6, IL-1beta, and TNF-alpha production in vitro have been reported in healthy elderly people. Cytokine gene polymorphisms have been demonstrated to be associated with cytokine production both in vivo and in vitro, and with some diseases. Thus, gene polymorphisms of cytokine may play a role in longevity by modulating an individual's responses to life-threatening disorders. Cytokine gene polymorphisms at IL1A-889, IL1B+3953, IL1B-511, IL1RN VNTR, IL6-174, IL10-1082, and TNFA-308 were genotyped in 250 Finnish nonagenarians (52 men and 198 women) and in 400 healthy blood donors (18-60 years) as controls. No statistically significant differences were found in the genotype distributions, allelic frequencies and A2+ carrier status of IL-1alpha, IL-1beta, IL-1RA, IL-6, IL-10, and TNF-alpha genes between nonagenarians and younger controls within Finnish population, nor between male and female nonagenarians. No differences emerged between nonagenarians and younger controls by comparing different IL-1 gene cluster haplotypes. Thus, there is no evidence of an association of IL-1 complex, IL-6, IL-10, and TNF-alpha gene polymorphisms with longevity, alone or in combination.

Adult↗
PubMed2001

Suppression of T-cell activation by Lactobacillus rhamnosus GG-degraded bovine casein.

Earlier data indicate that Lactobacillus rhomnosus GG ATCC 53103 (L. GG), a commensal intestinal bacterial strain, promotes the degradation of proteins in the gut in vivo, and bovine casein hydrolysed with L. GG-derived proteases suppresses lymphocyte proliferation in vitro. The present study aimed to evaluate the effect of L. GG-degraded bovine casein on T-cell activation, i.e. IL-2 mRNA expression and protein kinase C (PKC) translocation. To this end, Northern blot analyses for IL-2 mRNA expression and PKC assays with and without L. GG-degraded casein were carried out on T cells isolated from 11 healthy adults. Cell cultures in 8-11 experiments contained 1 mg ml(-1) bovine casein in degraded or undegraded form in the presence of a mitogen, i.e. phorbol 12,13-dibutyrate plus calcium ionophore (PBDu + A23187) or anti-CD3. Also IL-2, IL-4 and IFN-gamma syntheses were determined in 24-h culture supernatants. IL-2 mRNA expression was reduced in experiments with L. GG-degraded casein. In parallel, the IL-2 concentration in PBDu + A23187-stimulated culture supernatants, expressed as geometric means (95% confidence interval), decreased from 15,892 (7174-35,203) pg ml(-1) to 4744 (2095-10,742) pg ml(-1) when containing L. GG-degraded casein. L. GG-degraded casein inhibited PKC translocation, the action resembling that of PKC inhibitor, RO31-8220. These results extend previous data on L. GG-degraded casein, showing in vitro the suppression of T-cell activation.

Animals↗
PubMed2001

Allele 2 of interleukin-1 receptor antagonist gene increases the risk of thyroid peroxidase antibodies in subacute thyroiditis.

Subacute granulomatous thyroiditis (SAT) is a self-limiting systemic inflammatory disorder with possible transient expression of thyroid antibodies. Persistent hypothyroidism is uncommon. The interleukin-1 receptor antagonist IL-1ra is an inhibitor of IL-1 activity and allele 2 of the IL-1ra gene is associated with inflammatory diseases and IL-1ra production. Forty-eight subjects with SAT were investigated. Polymorphisms of IL-1ra, IL-1beta-511 and TNFalpha genes were studied with respect to thyroid peroxidase antibodies (TPOab), thyroglobulin antibodies, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Serum IL-1ra levels were measured. An increased allelic frequency (43% vs 22%, p=0.039) and carriage rate (79% vs 41%, p=0.018) for IL-1ra allele 2 were observed with expression of TPOab in 14 (29.2%) subjects compared with those with negative findings. The carriage rate for both IL-1ra allele 2 and IL-1beta-511 allele 2 was also increased with TPOab expression (71% vs 27%, p=0.004, respectively). No difference in allele frequency or carriage rate was found compared with healthy controls. Serum IL-1ra levels correlated with S-CRP (r=0.41, p=0.004) and ESR (r=0.34, p=0.016), but the association with genes or thyroid antibodies was statistically insignificant. S-CRP levels and ESR were lower and negatively correlated with expression of TPOab (r=-0.27, p=0.046 and r=-0.32, p=0.017). This study describes the multiplicity of the mechanisms responsible for the severity of the acute-phase response during the course of SAT. IL-1ra may have a significant anti-inflammatory role in SAT. Presence of IL-1ra allele 2 increases the risk of developing TPOab.

Adult↗
PubMed2001

Polymorphism of the cytokine genes in hospitalized patients with Puumala hantavirus infection.

BACKGROUND: Nephropathia epidemica (NE) is a mild type of haemorrhagic fever with renal syndrome caused by Puumala (PUU) hantavirus. The clinical course of NE varies from asymptomatic to fatal. The aim of this study was to establish whether polymorphisms in the cytokine genes are associated with susceptibility to and outcome of NE. METHODS: The genotypes of the genes of tumour necrosis factor alpha (TNFalpha), interleukin-1alpha (IL-1alpha), IL-1beta and IL-1 receptor antagonist (IL-1RA) were analysed by polymerase chain reaction in 87 subjects, all hospital-treated for serologically confirmed acute NE. The control group comprised 400 healthy blood donors. Nineteen out of these 400 (5%) controls were PUU virus-seropositive. RESULTS: IL-1RA allele 2 and IL-1beta (base exchange polymorphism at position -511) allele 2 were strongly associated with each other in both groups. NE patients were more often IL-1RA-2 negative/IL-1beta-2 negative than PUU-seronegative blood donors (38 vs 27%, odds ratio 1.65, 95% confidence interval 1.0-2.7). However, there were no differences in the clinical severity of NE between the IL-1RA-2 negative/IL-1beta-2 negative and the other patients. The other allele frequencies studied evinced no statistically significant differences between the groups. Thirty-three out of 87 (38%) patients and 121 out of 381 (32%) seronegative controls were carriers of the high-producer genotype TNF2 allele. Several parameters showed the clinical course of NE to be more severe in TNF2 carriers than in non-carriers. CONCLUSIONS: These data suggest that non-carriage of the IL-1RA allele 2 and IL-1beta (-511) allele 2 may contribute to susceptibility to NE. Furthermore, TNFalpha polymorphism seems to be associated with the outcome of NE.

Adolescent↗
PubMed2001

Elevated interleukin-6 plasma levels are regulated by the promoter region polymorphism of the IL6 gene in primary Sjögren's syndrome and correlate with the clinical manifestations of the disease.

OBJECTIVES: To determine whether plasma interleukin-6 (IL-6) and G/C base exchange polymorphism at position -174 of the IL6 gene have an effect on the clinical manifestations of primary Sjögren's syndrome (pSS). METHODS: Levels of circulating IL-6 protein and polymorphism of the IL6 gene were analysed in 66 patients with pSS and in 400 healthy subjects. These data were studied in relation to clinical data on the pSS patients. RESULTS: Plasma IL-6 was elevated in pSS patients compared with healthy controls. pSS patients with coeliac disease, pulmonary fibrosis or alveolitis or peripheral nervous system symptoms had significantly higher IL-6 levels than patients without these manifestations. IL-6 levels increased in parallel with the histological grade of minor salivary gland biopsy and the number of pSS criteria fulfilled. IL6 allele frequencies were similar in patients and normal subjects. Plasma IL-6 levels were regulated by the IL6 genotype in pSS patients. CONCLUSIONS: The G/C polymorphism of the IL6 gene does not predispose patients to pSS, but the circulating IL-6 concentration is related to specific manifestations of the disease and the levels of IL-6 are regulated by the IL6 promoter polymorphism in pSS.

Adolescent↗
PubMed2001

The promoter polymorphism of the interleukin-6 gene regulates interleukin-6 production in neonates but not in adults.

In the promoter region of the IL-6 gene there is a single base exchange (G --> C) polymorphism at position -174. Recent findings suggest that this polymorphism may affect the transcription rate of the IL-6 gene and IL-6 plasma levels. To analyse its biological significance, we examined IL-6 plasma levels in cord blood and IL-6 production by neonatal cells after LPS-stimulation in relation to the presence of the IL-6G and IL-6C alleles. We hypothesized that since healthy neonates lack a previous exposure to exogenous antigens, their cytokine production could be genetically regulated. We also assumed that the normal labour-related stress could provide a physiological stimulus for IL-6 production. Cord blood was collected from 50 healthy, full-term neonates after normal vaginal delivery (VD) and from 42 healthy, full-term neonates after elective caesarean section (ECS). Adult samples were obtained from 450 healthy adult controls. The -174 polymorphism was analysed using PCR. IL-6 plasma levels and in vitro IL-6 production were measured using an ELISA method. Generally, IL-6 plasma levels in neonates were significantly higher than those in adults (neonates born by VD versus adults p < 0.001 and neonates born by ECS versus adults p < 0.001); the median value for neonates born by VD was 11.4 pg/ml (4.5-45.9), for neonates born by ECS 2.9 pg/ml (1.9-6.4) and for adults, 1.2 pg/ml (0.7-2.0). Surprisingly, cord blood IL-6 levels after VD differed significantly from those after ECS (p < 0.001). An analysis was carried out to ascertain if there was a genetic association between different IL-6 genotypes and IL-6 plasma levels in neonates. In the group of VD neonates with the CC genotype, non-carriers of the G allele, secreted significantly more IL-6 than carriers of the G allele (p < 0.03); 21.4 pg/ml (9.5-81.3) and 9.6 pg/ml (3.5-36.2) respectively. In line with this, ECS newborns with the CC genotype had higher IL-6 plasma levels than carriers of the G allele (p < 0.02); respective median values were 6.3 pg/ml (2.2-12.9) and 2.7 pg/ml (1.7-4.1). These findings were also supported when in vitro IL-6 production by neonatal mononuclear cells was compared carriers of the G allele and non-carriers of the G allele. IL-6 levels were significantly lower in carriers of the G allele than in non-carriers (p < 0.04); respective median values were 6,980 pg/ml (4,175-16,800) and 17,425 pg/ml (11,400-33,900). In vivo or in vitro production of IL-6 of adult controls was not associated with the IL-6 -174 polymorphism. The difference between cord blood IL-6 levels after VD and after ECS suggests that normal labour-related stress induces IL-6 production. Our data also suggest that the -174 polymorphism of the IL-6 gene participates in the regulation of IL-6 responses in both groups of neonates. Furthermore, the naive IL-6 response of stimulated neonatal cells is associated with the -174 polymorphism of the IL-6 gene. In healthy adults, the regulation of IL-6 responses differs from that of healthy neonates, since baseline and inducible IL-6 levels in adults were not associated with this polymorphism. This indicates that the genetic regulation of IL-6 production can be observed in naive cells, while in adult cells previous contact with exogenous antigens probably modifies their responses.

Adult↗
PubMed2000

Interleukin-6 and interleukin-1 receptor antagonist in cerebrospinal fluid from patients with recent tonic-clonic seizures.

We have previously reported increased concentrations of interleukin (1L)-6 in CSF from patients with tonic-clonic seizures, where increased cytokine production most likely is a consequence of neuronal epileptic activity associated with seizures. The biological effects of IL-6 are mediated by other cytokines, which are studied here in addition to IL-6. The purpose of this study was to analyze levels of soluble cytokines from plasma and CSF from patients with newly developed tonic-clonic seizures. The concentrations of IL-6, IL-1 receptor antagonist (IL-1RA), IL-1beta, tumor necrosis factor (TNFalpha) and nerve growth factor (NGF) were measured from plasma and CSF from 22 patients with newly developed tonic-clonic seizures within 24 h from the seizure and 18 controls. The mean concentrations of IL-6 were significantly increased in CSF (P<0.001) and plasma (P<0.01) after tonic-clonic seizures, there was some indication of increased concentrations of IL-1RA and no significant change in NGF, IL-1beta or TNFalpha. Our study shows that cytokine network is activated in patients after recent tonic-clonic seizures. We provide evidence of intrathecal production of IL-6 associated with electrical seizure activity.

Adolescent↗
PubMed2000

Interleukin-10 generation in atopic children following oral Lactobacillus rhamnosus GG.

Oral Lactobacillus rhamnosus GG ingestion for 5 days to 4 weeks has been shown to alleviate clinical symptoms of gastrointestinal inflammation and atopic dermatitis. To determine whether oral Lactobacillus rhamnosus GG may act by generating immunosuppressive mediator in atopic children. Lactobacillus rhamnosus GG (ATCC 53103) at a daily dose of 2 x 1010 cfu was added for 4 weeks to the diets of nine children (mean age, 21 months) with atopic dermatitis. Blood and faecal samples were collected before supplementation and at early (2 weeks) and late stage (4 and 8 weeks from the beginning). The concentrations of interleukin-6 (IL-6), IL-10, IL-12, tumour necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma) in sera, as well as the production of IL-2, IL-4, IL-10 and IFNgamma in mitogen-induced peripheral blood mononuclear cells, were assessed. Secretory IgA and TNFalpha were also determined in faeces. The serum IL-10 concentration differed significantly between before, early and late samples (P < 0.001) due to the elevation of serum IL-10 in the later phase of oral Lactobacillus rhamnosus GG ingestion. The enhancement of IL-10 production in mitogen-induced cultures preceded the rise in serum IL-10. The enhanced IL-10 generation in vivo substantiates the anti-inflammatory properties of specific probiotic bacteria strains, and provides an additional reason for considering such treatments for patients with intestinal inflammation.

Animals↗
PubMed2000

Interleukin-1 beta, interleukin-1 receptor antagonist and interleukin-6 plasma levels and cytokine gene polymorphisms in chronic lymphocytic leukemia: correlation with prognostic parameters.

BACKGROUND AND OBJECTIVE: The growth of B-cell chronic lymphocytic leukemia (B-CLL) cells has been shown to be dependent on exogenous growth factors in vitro. We wanted to evaluate the clinical relevance of interleukin (IL)-6, IL-1 beta and interleukin-1 receptor antagonist (IL-1Ra) in B-CLL. As the plasma levels of IL-6, IL-1 beta and IL-1Ra have been suggested to be partly dependent on gene polymorphism, the previously described polymorphisms of the IL-1 complex genes and the IL-6 gene were also studied. DESIGN AND METHODS: The plasma levels of these cytokines were measured in a cohort of 36 patients with B-CLL and in 400 healthy subjects. The previously described polymorphisms of the IL-1 complex genes and the IL-6 gene were studied using PCR and RFLP. These data was correlated with other parameters associated with severity and prognosis of B-CLL and a number of clinical and laboratory findings. RESULTS: The plasma concentrations of IL-1 beta and IL-1Ra were lower in B-CLL patients than in normal controls (p < 0.001). The IL-1 beta plasma levels were dependent on the cell immunophenotype score and state of progression of the disease. Moreover, plasma concentrations of IL-6 were elevated in B-CLL patients compared with healthy subjects (p < 0.005) and correlated with disease stage, hemoglobin levels, anemia and erythrocyte sedimentation rate in the patients. The allele frequencies of the analyzed genes were similar in patients and controls. INTERPRETATION AND CONCLUSIONS: Our data demonstrate that in B-CLL, plasma levels of IL-1 beta, IL-1Ra and IL-6 differ from normal, and mechanisms other than allelic imbalance of their genes account for the distinct cytokine profiles observed in this disease.

Aged↗
PubMed2000

A rare allele combination of the interleukin-1 gene complex is associated with high interleukin-1 beta plasma levels in healthy individuals.

Increases in the plasma levels of the inflammatory cytokines can be detected in various infectious and inflammatory diseases, but in healthy individuals these levels are in most cases low or undetectable. There is now increasing evidence that genes of the inflammatory cytokines are polymorphic and the various alleles may differ in their capability to produce the cytokine. We have measured the plasma levels IL-1 beta of 400 healthy blood donors and correlated these to the genotype (biallelelic base exchanges at the position - 889 of the IL-1 alpha gene, and at the position - 511 of the IL-1 beta gene and the pentaallelic VNTR in the second intron of the IL-1Ra gene). The median concentration of IL-1 beta was 5.8 pg/ml (upper and lower quartiles 2.2-13.6). The polymorphisms of the IL-1 beta and IL-1 Ra genes did not have any significant influence on the IL-1 beta levels, but the IL-1 alpha 2.2 homozygotes (32/400 blood donors) had significantly elevated levels (median 7.0 pg/ml, quartiles 2.2-22.4, one-way ANOVA p < 0.008 as compared to the IL-1 alpha 1.1 homozygotes and p < 0.02 as compared to the IL-1 alpha 1.2 heterozygotes). This effect of IL-1 alpha 2.2 homozygosity was more pronounced in donors, who also were carriers of the IL-1 beta allele 2. Thus these data suggest that this allele combination has a regulatory effect on basal IL-1 beta production.

Adolescent↗
PubMed1999

Induction of beta-2-microglobulin release in vitro by chronic lymphocytic leukaemia cells: relation to total protein synthesis.

The in vitro production of beta2-M by B-CLL cells from 27 patients was investigated. In all cases, low spontaneous beta2-M release was observed. The production of beta2-M was enhanced to various extents when induced with 13 different stimulants and their combinations including IL-2, TNFalpha, SAC and TPA. Beta2-M release was 3.8-fold (range from 1.9 to 9.2-fold) in cultures stimulated with TPA (10 ng/ml), compared with the spontaneous release, and even faster if TNFalpha or IL-2 were added. A strong correlation was revealed between beta2-M production and the total protein synthesis of leukaemic cells when the latter was assessed using 14C-L-leucine incorporation. Hence, both beta2-M release and leucine incorporation are promising activation markers for CLL B-lymphocytes.

Aged↗