Biomedical subjects

Mikko Hurme

Publications and source records attributed to Mikko Hurme.

42 records · Page 3Linked to original sources

PubMed2002

The IL1A genotype associates with atopy in nonasthmatic adults.

BACKGROUND: The skin prick test is used to examine specific IgE-mediated allergic responses. Generally, results accord well with anamnestic information on atopy. Several genetic factors probably affect the strength of allergen-mediated skin test reactions. OBJECTIVE: We sought to investigate skin test findings in a population-based sample of adult asthmatic patients and control subjects and to establish whether the IL1A genotype affects allergy testing. METHODS: We analyzed the single G-to-T base exchange polymorphism in exon 5 at +4845 of the gene encoding IL-1alpha (IL1A) in adult asthmatic patients (n = 245) and nonasthmatic control subjects (n = 405). The data were assessed for correlation with data on the skin test responses of these subjects to 22 common allergens. RESULTS: The IL1A genotype distribution and allele frequencies proved similar in patients and control subjects. Surprisingly, the IL1A genotype distribution was markedly different in control subjects with positive (ie, >/=1 positive reaction) and negative skin test responses (P =.006). This difference was caused by an increase in the frequency of the rarer allele 2 in control subjects with negative skin test responses (P =.004). CONCLUSION: Our study demonstrates that the IL1 gene complex is involved in the regulation of IgE-mediated atopic reactions. The results suggest that skin test responses to specific allergens are differently regulated in nonasthmatic and asthmatic subjects. Because of the potential role of the IL1A genotype as a confounding factor in skin prick testing, these results require special attention and should be further evaluated in other clinical settings.

Adult↗

PubMed2002

Polymorphism of the IL-10 gene is associated with susceptibility to herpes zoster.

Herpes zoster (HZ) is induced by diseases or medical treatments leading to a decrease in cell-mediated immunity, but in most cases it appears without any detectable, predisposing condition. We report here that susceptibility to HZ is genetically determined. The promoter region of the IL-10 gene contains 3 single-nucleotide polymorphisms (G/A at -1082, C/T at -819 and C/A at -592) which form 3 haplotypes, GCC, ACC and ATA. These haplotypes are known to differ in terms of their effect on the transcription of the IL-10 gene. In a cohort of 60 HZV patients, the number of carriers of the ATA haplotype was 32 (53%), while in blood donors the frequency was 151/400 (38%) (p < 0.05).

Adolescent↗

PubMedDate not supplied

The balance of inhibitory and excitatory cytokines is differently regulated in vivo and in vitro among therapy resistant epilepsy patients.

PURPOSE: Excessive neuronal activity and seizures directly stimulate cytokine expression. In this study we investigated cytokine production in circulating blood and peripheral blood mononuclear cells (PBMC) in order to assess the cellular origin of these cytokines in patients with therapy resistant epilepsy. METHODS: We compared the levels of plasma IL-1beta, IL-1Ra and IL-6 in 10 patients with therapy resistant localization-related epilepsy and in healthy volunteers. The spontaneous and exogenously stimulated production of these cytokines was studied in PBMC cultures using EIA. Moreover, cell-specific cytokine production was studied using flow cytometry. RESULTS: Highly pro-inflammatory cytokine profile (high IL-6, low IL-1Ra and low IL-1Ra/IL-1beta ratio) was observed in plasma from patients with epilepsy. Spontaneous and LPS stimulated cytokine release was similar in PBMC cultures of patients and control subjects. When cells were stimulated with OKT3 the cytokine response profiles in patients with epilepsy were almost opposite (anti-inflammatory) to the profile which was observed in circulating blood. Low IL-6 was observed in cell cultures of patients when stimulated with PDBu + A23187. Flow cytometric analysis revealed that the percentages of IL-1beta, IL-1Ra and IL-6 positive monocytes were similar in patients and control subjects. CONCLUSIONS: Patients with therapy resistant epilepsy display a pro-inflammatory profile of plasma cytokines without any evidence of increased production from PBMC. These results suggest that the most likely origin for these cytokines is the brain, where cytokines can exert neuromodulatory functions.

Adolescent↗

PubMedDate not supplied

IgA levels are predictors of mortality in Finnish nonagenarians.

It has been demonstrated that in obviously healthy, very old people increased levels of inflammatory markers as well as some defects in T lymphocyte populations are strong predictors of mortality. Very little is known about the role of possible functional defects in antibody formation. To examine this, we now measured IgM, IgG and IgA concentrations in a cohort of 285 nonagenarians (67 males, 218 females). IgG and IgA levels were significantly higher than those of healthy middle-aged controls. The analyzed serum samples were taken at the age of 90-91 years. After 4 years, 20 males and 94 females had survived. To analyze the role in predicting mortality, the immunoglobulin data (as well as the measured CRP and IL-6 concentrations) were stratified according to this survival data. IgA levels (and CRP and IL-6 levels) were clearly higher in the nonsurvivors than in the survivors. These data imply that elevated serum IgA level, i.e. indicator of intestinal inflammation and/or defect in mucosal defence, is a strong mortality predicting factor.

Age Factors↗

PubMedDate not supplied

The combination of the interleukin-1alpha (IL-1alpha-889) genotype and the interleukin-10 (IL-10 ATA) haplotype is associated with increased interleukin-10 (IL-10) plasma levels in healthy individuals.

Family studies have demonstrated striking differences between individuals in their ability to produce IL-10 following lipopolysaccharide (LPS) stimulation of whole blood cultures in vitro, suggesting that differences in IL-10 production involve a considerable hereditary component. The first aim of this study was to analyse the possible effect of IL-10 genotypes and haplotypes on IL-10 plasma levels in a healthy Finnish population. As previous reports have demonstrated that endogenously produced IL-1 induces LPS-stimulated IL-10 production and that IL-10 inhibits synthesis of IL-1 in human monocytes, it is apparent that these two cytokines form an autoregulatory feedback loop. Secondly, we were interested whether any relationship could be found between IL-10 and IL-1beta in vivo. To examine this, the influence of IL-1alpha -889, IL-1beta -511 and IL-1Ra VNTR genotypes and IL-10 genotypes/haplotypes (ACC, GCC and ATA) on IL-10 plasma levels, and a putative correlation between IL-10 and IL-1alpha plasma levels were analysed. Four hundred adult blood samples were obtained from the Finnish Red Cross Blood Transfusion Centre, Tampere. The IL-10, IL-1alpha, IL-1beta and IL-1Ra gene polymorphisms were analysed using PCR. IL-1beta and IL-10 plasma levels were measured using an ELISA method. Our results indicated that increased IL-10 plasma levels were associated with the ATA haplotype (p = 0.03) and, surprisingly, with the IL-1alpha allele 2 carrier status (p = 0.02) in healthy individuals. This IL-1alpha 2+/ATA+ combination was found in 93 subjects out of 400 analysed (23%) and was associated with significantly high IL-10 plasma levels (p = 0.002). When individuals were classified into three groups, with no detectable IL-10 plasma levels (n = 145), with moderate levels (n = 152) and with high levels (n = 100) of IL-10, the IL-1alpha2+/ATA+ combination was more likely present among those with high levels than among those with undetectable levels of IL-10 (OR = 3.3, 95% CI 1.8 - 6.0, p < 0.001) or those with moderate levels of IL-10 (OR = 2.0, 95% CI 1.2 - 3.6, p = 0.012). Besides the observed association between IL-1alpha genotype and IL-10 levels, a moderate correlation was found between IL-10 and IL-1beta levels (r = 0.6, p = 0.01) among IL-10 producers (n = 252). The present findings suggest that the genotype combination of IL-1alpha 2+/ATA+ has a regulatory effect on basal IL-10 levels and that among individuals with measurable IL-10 plasma levels, IL-1beta and IL-10 basal levels correlate. Until now, data on the feedback loop between IL-1 and IL-10 cytokines have been based on studies in vitro, but now our results suggest that this relationship may also exist in vivo.

Genotype↗

PubMedDate not supplied

Interleukin 1B gene polymorphism is associated with baseline C-reactive protein levels in healthy individuals.

C-reactive protein (CRP) is a sensitive marker of inflammation induced by both IL-6 and IL-1. Thus, genetic variation in these genes could be associated with the variety in C-reactive protein levels, and therefore with the severity of the entire inflammatory response. Even a subtle elevation in baseline CRP levels in healthy individuals has been found to significantly increase the risk for cardiovascular diseases. Therefore, to find out the possible role of pro-inflammatory cytokines in CRP baseline regulation we conducted a study of 338 healthy blood donors whose CRP levels were determined and whose single nucleotide polymorphisms of IL1A(C/T)-889, IL1B(C/T)-511, IL1B(C/T) + 3954, IL6(G/C)-174 and ILRN (a VNTR) both genotyped and haplotyped. The data revealed an association between CRP levels and the IL1B + 3954 genotype. Also, the bilocus haplotype IL1B-511*1/IL1B + 3954*2 was more frequent in subjects with below median CRP levels (< 0.72 mg/l), and composite genotype analysis of IL1B-511/IL1B + 3954 supported this finding. Our findings suggest that in healthy people, basal CRP levels are regulated by IL1B but not by IL6 genetics.

Adult↗