Comparison of a Chronotherapeutically Administered β Blocker vs. a Traditionally Administered β Blocker in Patients With Hypertension

Increasing systolic blood pressure and heart rate during the early morning results in increased myocardial oxygen demand. The use of β blockers during this period may decrease cardiac workload, particularly in β-blocker sensitive patients. The impact of a new chronotherapeutic β blocker was assessed in 44 hypertensive patients. Patients were randomized to delayed-release propranolol (INP) dosed at 10 p.m. or to traditionally dosed propranolol (ILA) dosed at 8 a.m. for 4 weeks, following which they were switched to the alternative formulation for 4 weeks. Thirty-four-hour ambulatory blood pressure monitoring and pharmacokinetic measurements were obtained. INP and ILA resulted in significant reductions in mean 24-hour blood pressure (−9.01-6.9 mm Hg and −10.41-7.7 mm Hg, respectively). The top 25% of responders to highdose propranolol (sensitive patients) were compared on each formulation. Mean trough reductions were −8.0/-6.7 mm Hg and −7.61-5.8 mm Hg, respectively. Mean blood pressure reductions in the β-blocker sensitive patients (n=11) between 6 a.m. and noon were −15.2/-11.9 mm Hg on INP and -8.0/-4.6 mm Hg on ILA. Heart rate reduction was −14.1 bpm and double product reduction was −3319 in the INP patients between 6 a.m. and 12 noon compared with −10.5 and −2209 in the ILA patients. This study suggests that INP and ILA are effective once-a-day β blockers, but the use of delayed-release propanolol results in a greater reduction in double product between 6 a.m. and noon in β-blocker sensitive patients than does traditionally dosed propranolol.     

Association of amino acid variation (Trp64Arg) in the beta3-adrenergic receptor gene with bone mineral density

Background:   Recent studies have revealed that a mis-sense mutation replacing tryptophan with arginine at codon 64 (Trp64Arg) of the beta3-adrenergic receptor ( β3-AR ) gene was associated with insulin resistance in non-diabetic subjects and to earlier onset of non-insulin dependent diabetes mellitus. To analyze a possible involvement of β3-AR in bone metabolism, we investigated the association between bone mineral density (BMD) and the Trp64Arg polymorphism.
Methods:  A large cohort of Japanese postmenopausal women comprised the study population. The genotypic frequencies in this cohort were Trp/Trp, 61.8%; Trp/Arg, 33.2%; and Arg/Arg, 5.0%.
Results:  When the subjects were separated into two groups, one bearing at least one Trp allele at codon 64 (Trp/Trp and Trp/Arg) and the other with none (Arg/Arg), the former subjects had significantly higher Z scores for total-body BMD (mean ± SD, 0.432 ± 0.93 versus −0.135 ± 0.93; P  = 0.033).
Conclusions:   These data suggested an association between this single-nucleotide polymorphism (SNP) in the β3-AR gene and BMD, and therefore a possible involvement of the Arg allele (or the absence of Trp64) in postmenopausal osteoporosis among Japanese women.     

Genetic and Biochemical Heterogeneity of β-Thalassaemia in Naples

S ummary We have investigated 32 children with Cooley's anaemia from Naples, Italy. Criteria for inclusion in the study were: (a) typical clinical and haematological findings; (b) absolute transfusion requirement; and (c) elevated Hb A₂ in both parents. From biosynthetic studies we have established that five children (including two sets of sibs) had β° thalassaemia, while the rest had β⁺ thalassaemia. Thus, the frequency of β⁺ thalassaemia among unrelated patients was about 90%. The distribution of β/α ratios among β⁺ patients ranged from 0·01 to 0·16 and it was bimodal, consistent with some of them having a β°/β⁺ genotype and others a β⁺/β⁺ genotype. The distribution of β/α ratios of the patients' parents (obligate heterozygotes) ranged from 0·24 to 0·73, and it was plurimodal, consistent with the coexistence in this population of multiple β thalassaemia alleles, of which one must be β° and at least one is β⁺. A systematic analysis of 20 families indicates that the β/α ratio is to some extent quantitatively inherited, and its suggests non-randomness in the assortment of β thalassaemia alleles that can give rise to a Cooley's phenotype.     

Angiotensinogen gene haplotype is associated with the prevalence of Japanese non-alcoholic steatohepatitis

Aim: Non-alcoholic steatohepatitis (NASH) patients frequently have hypertension, which is considered to be an important predictive factor for the subsequent development of hepatic fibrosis. The renin-angiotensin system is also known to contribute to the progression of NASH. Various types of functional single-nucleotide polymorphisms (SNPs) involved in the development of NASH have been proposed. Angiotensinogen (AGT) gene SNPs related to cardiovascular diseases have been reported. We aimed to evaluate the involvement of the AGT gene haplotype in Japanese NASH patients. Methods: Previously described genotypes of SNPs of the AGT gene, rs4762 C/T polymorphism (T207M), rs699 C/T polymorphism (T268M), and rs7079 C/A polymorphism (C11537A), were determined in 124 Japanese biopsy-proven NASH patients and 150 healthy volunteers (controls). Results: The allele and genotype frequencies in rs4762 and rs699 SNPs in NASH patients were similar to those in controls, while the frequency of the A allele and A/- genotype in rs7079 SNPs were much higher in NASH patients than in controls. In addition, the 3-SNP haplotype CTA was significantly over-represented in NASH patients compared with controls. Regarding clinical features of NASH patients, diastolic blood pressures in patients with the CTA/- genotype were much higher than in patients with other genotypes. Conclusions: We found a 3-SNP haplotype of the AGT gene that is involved in the development of NASH and influences hypertension in NASH patients. These results provide new insight into the therapy of NASH patients with the CTA haplotype using ACE inhibitors or angiotensin II type 1 receptor blockers.     

α and β thalassaemia among Chinese children in Guangxi Province, P.R. China: molecular and haematological characterization

Summary We have studied nearly 100 patients with β thalassaemia major and 60 patients with Hb H disease who were attending the Haematology Clinic of Guangxi Medical College. Treatment of the patients was limited and only a few patients with β-thalassaemia major received blood transfusion(s). As a result, the severe anaemia has led to early death at 3–4 years for β⁺-thalassaemia homozygotes, and 8–12 years for β⁺-thalassaemia homozygotes. Four β-thalassaemia alleles are responsible for nearly 90% of all β-thalassaemia chromosomes. This information has resulted in the initiation of a prenatal testing programme at the local level. The patients with Hb H disease maintained a haemoglobin level of 6–10 g/dl and early death was infrequently observed. The ^SEA deletion was the major type of α-thalassemia-1, while three smaller deletions (−2.7, −3.7 and −4.2 kb) and two nondeletional α-thalassaemia determinants (Hbs Constant Spring and Quong Sze) were the α-thalassaemia-2 types.     

(β-Adrenergic receptor subtypes in human pineal gland

Abstract: The secretion of melatonin by the pineal has been promoted as a direct monitor of adrenergic function in depressive illness. However, discrepant findings have been reported, possibly reflecting a complex adrenergic regulation of pineal output. In order to clarify the anatomical localization and relative density of β-adrenergic receptors and their subtypes in human pineal, quantitative autoradiographic analysis was conducted of β-adrenergic receptors in postmortem specimens using the high affinity radioligand ¹²⁵I-pindolol. Dense specific binding was found throughout the gland. β₁,-adrenergic receptors were more numerous, but β₂-receptors were present in an overlapping anatomical distribution with β₁-receptors.     

Intravenous natural β-interferon in white patients with chronic hepatitis C who are nonresponders to α-interferon

Objectives: α-Interferons (α-IFN) have been shown to be effective in the treatment of chronic viral C hepatitis, but their efficacy remains unsatisfactory. Recently natural β-interferon (β-IFN) administered by intravenous infusion has been used successfully.
Methods: To evaluate the efficacy and safety of intravenous β-IFN administration we treated 20 patients with histologically proven chronic hepatitis C who were nonresponders to at least two previous courses of α-IFN treatment. All patients received 6 million units (MU) of natural human fibroblast β-IFN by drip infusion, 6 times per wk for 8 wk and were followed up for 6 months after suspension of treatment.
Results: Five patients (25%) had response at the end of treatment; of these patients only one had sustained response. Patients who responded to therapy had lower, although not significantly, baseline levels of HCV RNA, compared with nonresponders. Whereas mean viral load decreased during therapy, only two patients were HCV RNA negative at the end of treatment, but none were at the end of the follow-up period. Genotype 1 was found in 17 cases, genotype 2 was found in one case, and a combination of genotypes 1b and 2a was found in the remaining two cases. Therapy was well tolerated and β-IFN administration was neither interrupted nor its dosage reduced due to side effects in any of the patients.
Conclusions: Our study shows that intravenous β-IFN is well tolerated and that the modest results obtained may depend on the brevity of treatment. Consequently, further studies are needed to define the optimum dose, schedule, and duration of treatment to eradicate HCV infection.     

Molecular analysis of the Turkish form of deletion-inversion (δβ)° thalassaemia

Two unrelated (δβ)°-thalassaemia patients from Southern Turkey are presented. DNA studies indicated that both of them are homozygous for the Turkish type of (δβ)°-thalassaemia characterized by one large deletion of 11.5 kb including the δ and β globin genes at the 5' end and one small deletion of 1.6 kb at the 3' end, which are separated by an inverted 7.6 kb long DNA segment that includes L1 repetitive sequence. In the present study a PCR-based method was performed to produce a unique deletion-specific product and subjected to sequence analysis for the determination of the breakpoint. DNA polymorphisms in the β-globin gene cluster of deletion-inversion type of (δβ)°-thalassaemia, IVS-I-6 and β-39 globin genes were examined. Analysis of sequence variations in regulatory regions including the 5' hypersensitive site-2 of the locus control region (LCR), the δ, ^Gγ and ^Aγ 5' flanking regions and the second intervening sequence (IVS-II) of ^Aγ and ^Gγ genes indicated the presence of close similarities between the chromosome carrying the Turkish form of deletion-inversion δβ)°-thalassaemia and the chromosome associated with β-39 nonsense mutation in haplotype II. These two chromosomes are characterized by the presence of a 4 base pair deletion in the ^Aγ^T globin gene promoter. A C → T alteration at position −199 5' to the δ gene was also found to be associated with the Turkish type of (δβ)°-thalassaemia and β-39 chromosome.     

Five haplotypes in Black β-thalassaemia heterozygotes: three are associated with high and two with low Gγ values in fetal haemoglobin

Genotypes at seven different polymorphic restriction sites (5'to the ° gene, at the ^G γ, at the ^A γ, at the Ψβ , 3'to the Ψβ , at the β , and 3'to the β genes) were analysed by restriction endonuclease mapping of the DNA from 66 Black β -thalassaemia heterozygotes from Georgia and several of their normal relatives. Five different haplotypes were observed. Three of these were associated with high ^G γ values in the small amount of Hb F (0.8-8.3%) present in the blood of these patients and two with low ^G γ values. One haplotype [- + - ++++] that occurred on two of every three β thalassaemia chromosomes was associated with high ^G γ levels, and is the same as that found in some Black SS patients also having high ^G γ values (Gilman & Huisman, 1984). Two others [- ++ - + - +] and [−+−−+++] were also associated with high ^G γ, while two [−−−−+++] and [+−−−−++] were associated with low ^G γ. Variation in haematological data, mainly MCV and MCH values, was found to be caused in part by the type of β -thalassaemia (defined by its haplotype) and by the presence of an additional α-thalassaemia-2 heterozygosity or homozygosity.     

A NEW DNA POLYMORPHISM IN THE β-GLOBIN GENE CLUSTER CAN BE USED FOR ANTENATAL DIAGNOSIS OF β-THALASSAEMIA

S ummary . Restriction endonuclease analysis of the human β-globin gene cluster has revealed a new DNA polymorphism at a Pvu II recognition site approximately 3.5 kilobases from the 3' end of the ^Aγglobin gene. In patients from the Mediterranean area, the Pvu II polymorphism was associated equally with both normal and β-thalassaemia chromosomes. In patients of Indian and Pakistani origin the polymorphism was almost exclusively associated with only the normal chromosome. Therefore this site may prove very useful for the antenatal diagnosis of β-thalassaemia by acting as a genetic marker for the normal chromosome in linkage analysis of family members.     

Polymorphism of Tumor Necrosis Factor-β and Alcohol Dehydrogenase Genes and Alcoholic Brain Atrophy in Japanese Patients

Background: Alcohol abuse can induce brain atrophy, but it only occurs in some alcoholics. Many inflammatory cytokines such as tumor necrosis factor (TNF) are produced rapidly in the brain by experimental or clinical injury.
Method: To investigate whether genetic polymorphism of TNF was related to alcoholic brain atrophy, we determined restriction fragment-length polymorphisms of the TNF-β genes in 72 male alcoholics. Computed tomography was used to determine the severity of brain atrophy.
Results: Digestion with Nco I and Msp I after polymerase chain reaction amplification showed that the TNFB¹ allele frequency was significantly higher in patients with brain atrophy than in those without brain atrophy (χ²= 10.20, p = 0.0034). A multivariate analysis that included age, total alcohol intake, ADH2 genotype, and TNF-β genotype showed that the ADH2¹/2¹ genotype and TNFB¹/B¹ genotype are independently associated with alcoholic brain atrophy. These findings suggest that the TNFB¹ allele may be associated with alcoholic brain atrophy.     

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

Background Interleukin-1β (IL-1β) 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-1β polymorphisms. Methods We examined 48 patients with reflux esophagitis and 96 control subjects, 89 with gastric cancer. IL-1β-511C/T genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results The frequency of IL-1β-511T alleles was significantly higher in reflux esophagitis patients (57.3%) than in controls (41.1%) (P = 0.0215, χ² = 5.289). The frequency of IL-1β-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-1β-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. Conclusions IL-1β-511T was associated with reflux esophagitis having hyperacidity. Differences of genetic background regarding gastric acid secretion may exist between Japanese and Caucasians.     

Association between a promoter polymorphism of the paraoxonase PON1 gene and pathologically verified idiopathic Parkinson's disease

Background:  Exposure to pesticide is associated with an elevated risk of Parkinson's disease (PD). Oxidative stress is also implicated in the etiology of PD. Paraoxonase (PON1) detoxifies organophosphates and exhibits antioxidant properties. It was postulated that polymorphisms of the PON1 gene lead to increased risk of PD.
Methods:  The seven polymorphisms of the PON1 gene were typed and neuropathologic examination performed in 360 Japanese people (191 men and 169 women) consecutively autopsied at a general hospital.
Results:  Thirty-three patients (18 men and 15 women) were diagnosed with pathologically verified idiopathic PD (pviPD). The proportion of male patients with pviPD was highest in the AA genotype (29.4%) of the G(−824)A polymorphism, followed by the GA genotype (9.3%), and least in the GG genotype (6.0%). These genotypic distributions and allele frequency were significantly different between male patients with and without pviPD ( P  = 0.021 and P  = 0.012, respectively). The odds ratio for the −824 A allele versus the −824G allele was 2.47 (95% CI 1.23–4.96). No association between pviPD and the PON1 polymorphisms was found in the female patients.
Conclusion:  Possession of the −824A allele may increase the risk of PD in Japanese men.     

白细胞介素-1B-511单核苷酸多态性与胃癌关系的流行病学研究

目的研究中国胃癌高、低发区白细胞介素（IL）-1B-511单核苷酸多态性、幽门螺杆菌（Hp）感染与胃癌的芙系。方法胃癌高发区（陕西省）胃癌患者、健康志愿者各102例，胃癌低发区（广东省）胃癌患者、健康志愿者各104例，两组人群在性别比及年龄上均匹配。采用限制性片段长度多态性（PCR—RFLP）分析IL-1B-511单核苷酸多态性，酶联免疫吸附法（ELISA）检测血清抗Hp—IgG抗体。结果在胃癌低发区，胃癌患者IL-1B-511T／T基因型频率明显高于对照人群（26．9％比13．4％，X^2=5．85，P〈0．05；OR=2．37，95％CI为1．16～4．82）。在胃癌高发区，胃癌患者IL-1B-511 T／T基因型频率与对照人群尢明显差异（27．5％比24．5％，X^2=0．41，P〉0．05）；高发区对照人群的IL-1B-511 T／T基因型频牢明显高于低发区相应人群（24．5％比13．4％，X^2=4．1，P〈0．05）。Hp感染轻度增加低发区人群发生胃癌的危险性（OR=3．03，95％CI为1．61～5．71），而IL-1B-511 T／T基因型增加Hp感染后胃癌发生的危险性（OR=8．0，95％CI为1．39～35．7）。结论IL-1B-511 T／T基因型与中国人胃癌发生有关，IL-1B-511 T／T基因型增加HP感染后胃癌发生的危险性。     

Study of Alzheimer's disease using transgenic mice: The mechanism of formation of brain Aβ amyloid and neurofibrillary tangles

Background:   The purpose of the present paper was to clarify the role of brain amyloid β protein (Aβ) in Alzheimer's disease (AD) with the eventual aim of developing new treatments.
Methods:   Three kinds of transgenic mice (Tg) were examined: those overexpressing βAPP695ΔNL (APPsw mice), those expressing the R406W mutant form of human 4-repeat tau (tauR406W mice), and those with both βAPP695ΔNL and R406W mutant tau (APPsw × tau R406 double Tg).
Results:   First, cored plaques, diffuse plaques and amyloid angiopathy were detected in the brains of APPsw mice. Loss of neurons and synapses was seen in the cored plaques, and accumulation of phosphorylated-tau in dystrophic neurites around the cored plaques. However, Neurofibrillary tangles were not seen. These mice displayed memory impairment and decreased levels of acetylcholine in the cortex and hippocampus. Second, tau R406W mice were produced. These mice developed motor disturbances and memory impairment, accompanied by gliosis and marked tau accumulation in neurons of the frontotemporal cortex, hippocampus and amygdala. No Aβ was detected. Third, APPsw × tauR406W double Tg were produced. The pattern of Aβ deposition was similar in these double Tg and the APPsw mice. Gallyas silver-staining showed greater levels of tauopathy in the hippocampus in these double Tg compared to the tauR406W mice.
Conclusion:   These findings suggest that deposition of brain Aβ is the initial event leading to subsequent disease such as accumulation of phosphorylated tau, neuronal loss and memory disturbance, and that the treatment of brain Aβ should be the first priority in finding a cure for AD.     

PPARγ Pro12Ala Pro/Pro and resistin SNP-420 G/G genotypes are synergistically associated with plasma resistin in the Japanese general population

Objective  The Ala allele of the Pro12Ala polymorphism (rs1801282) of peroxisome proliferator-activated receptor γ (PPARγ) is protective against type 2 diabetes (T2DM). Resistin, secreted from adipocytes, causes insulin resistance in rodents. Resistin gene expression is reduced by the PPARγ ligand. We previously reported that subjects with the G/G genotype of a resistin gene single nucleotide polymorphism (SNP) at –420 (rs1862513) had the highest circulating resistin levels, followed by C/G and C/C. The aim of this study was to determine the relationship among PPARγ Pro12Ala polymorphism, resistin SNP-420, and plasma resistin.
Design, patients and measurements  We cross-sectionally analysed 2077 community-dwelling subjects attending an annual medical check-up. Genotypes were determined by TaqMan analysis. Fasting plasma resistin was measured using ELISA.
Results  Plasma resistin appeared to be higher in subjects with the Pro/Pro genotype of PPARγ than those with Pro/Ala and Ala/Ala genotypes (mean ± SE, 11·6 ± 0·2 vs. 10·4 ± 0·5 μg/l). Multiple regression analysis, adjusted for age, gender, BMI, and resistin SNP-420, revealed that the Pro/Pro genotype was a positive predictor of plasma resistin (PPARγ ,  Pro/Pro vs. Pro/Ala + Ala/Ala, unstandardized regression coefficient (β) = 1·03, P  = 0·0384). The effects of the Pro/Pro genotype of PPARγ (Pro/Pro vs. Pro/Ala + Ala/Ala) and the G/G genotype of resistin SNP-420 (G/G vs. C/C) on plasma resistin were synergistic (β = 4·76, P  = 0·011).
Conclusions  The PPARγ Pro12Ala Pro/Pro and resistin SNP-420 G/G genotypes were synergistically associated with plasma resistin, when adjusted for age, gender, and BMI, in the Japanese general population.     

卵磷脂胆固醇酰基转移酶基因608C/T和511C/T多态性与湖南地区汉族人卒中的关系

目的 探讨卵磷脂胆固醇酰基转移酶(1ecithin cholesterol acyltransferase,LCAT)基因608C/T和511C/T多态性与中国湖南地区汉族人群卒中发病的关系.方法 选择150例脑梗死、150例脑出血患者以及122名年龄和性别相匹配的对照者,应用聚合酶链反应、单链构象多态性技术和限制性片...     

Hepatic 11beta-HSD1 mRNA expression in fatty liver and nonalcoholic steatohepatitis

Context  Nonalcoholic fatty liver disease represents the hepatic manifestation of the metabolic syndrome. Nonalcoholic steatohepatitis (NASH) is the progressive form of liver injury. The pathophysiology that leads to NASH is not well understood.
Objective  We hypothesize that an altered cortisol metabolism in the liver may be a pathogenetic factor.
Design and patients  75 patients (28 men, 47 women) underwent liver biopsy for elevation in liver enzymes. Histological diagnosis identified normal liver in eight, fatty liver in 20, NASH grade 1 in 22, grade 2 in nine, grade 3 in three patients, and other forms of hepatitis or cirrhosis in 13 patients. We quantified hepatic 11β-hydroxysteroid dehydrogenase type1 (11β-HSD1) and hexose-6-phosphate-dehydrogenase (H6PDH) mRNA expression by real-time PCR. In addition, analysis of 24 h urinary excretion of cortisol metabolites using GCMS was performed and compared with healthy controls.
Results  11β-HSD1 mRNA expression correlated significantly ( R ²= 0·809; P  < 0·001) with H6PDH mRNA expression, negatively with waist-to-hip ratio in women ( R ²= 0·394; P = 0·005), but not with urinary (THF + 5α-THF)/THE ratio, total cortisol metabolite excretion, age, BMI, degree of fatty liver or NASH stages. Total cortisol metabolite excretion was increased in patients with fatty liver or NASH compared with healthy controls.
Conclusions  Our data suggest that expression of hepatic 11β-HSD1 and H6PDH are closely interlinked. 11β-HSD1 gene expression does not seem to be involved in the pathogenesis of fatty liver or NASH. However, those patients showed an increased 5α- and 5β-reduction of cortisol leading to an increased cortisol turnover rate and an activation of the HPA axis.     

The prevalence of non-classic adrenal hyperplasia due to 11β-hydroxylase deficiency among hirsute women in a Turkish population

OBJECTIVE  The present study was designed to determine the prevalence of 11β-hydroxylase deficiency in adult women with hirsutism in a Turkish population.
DESIGN AND PATIENTS  One hundred and twenty-four consecutive unselected hirsute patients were studied. An ACTH stimulation test was performed in the midfollicular phase of the cycle on the patients and 20 age-matched controls by administration of a single bolus of 0.25 mg ACTH (1–24) at 0900 h.
MEASUREMENTS  Serum 11-deoxycortisol levels were measured before, 30 and 60 minutes after ACTH injection. Basal free testosterone (fT), SHBG, cortisol and androstenedione (A) were also measured. The diagnosis of 11β-hydroxylase deficiency has been presumed when the serum 11-deoxycortisol response to ACTH stimulation exceeded three times the 95th percentile of controls.
RESULTS  Basal hormone levels including fT and A were significantly higher in the hirsute women than in the healthy women. SHBG was significantly lower in the hirsute patients. Basal and ACTH stimulated 11-deoxycortisol levels were found to be significantly increased in the patients compared with the controls. Eight patients (6.5%) had an 11-deoxycortisol response higher than three times the upper normal limit.
CONCLUSIONS  Using stringent diagnostic criteria, we have found that 6.5% of the hirsute women in a Turkish population could be presumed to have 11β-hydroxylase deficiency.     

Circulating Soluble Interleukin-2 Receptor α and β Chain in Inflammatory Bowel Disease

Objectives : Inflammatory bowel disease is characterized by T cell activation. Activated T cells shed interleu-kin-2 receptors (IL-2R) in a soluble form. A positive correlation between sIL-2Rα (CD25) and disease activity in inflammatory bowel disease has been shown previously, whereas IL-2Rβ (CD122) has never before been investigated in this respect. Serum from 27 patients with ulcerative colitis (UC), 31 with Crohn's disease (CD), and 29 healthy volunteers was obtained. Methods : Disease activity was scored according to a semiquantitative score for UC and by Crohn's disease activity index for CD. sIL-2Rα and -β chains were assessed by a sandwich ELISA technique using monoclonal antibodies specific for CD25 and CD122, respectively. Results : The median concentration of sIL-2Rα was 4424 pg/ml in healthy controls, 6460 in UC ( p < 0.004), and 6371 in CD ( p < 0.01). The corresponding value of sIL-2Rβ in healthy volunteers was 605 pg/ml; in active UC, significantly lower levels were found at 233 pg/ml ( p < 0.01), whereas in inactive UC, no such difference was observed at 725 pg/ml ( p > 0.05). In CD, the levels were 839 pg/ml in inactive and 920 pg/ml in active disease stages ( p > 0.05 vs controls). A positive and significant correlation existed between sIL-2R levels of α and β chains in CD ( r = 0.64; p < 0.01) but not in UC ( r = -0.32; p > 0.05) or in healthy volunteers ( r = 0.16; p > 0.05). Conclusion : Future longitudinal studies will be necessary to learn whether this newly assessed sIL-2Rβ (CD122), which may interfere with IL-15R, could be used to predict disease exacerbation and to monitor anti-inflammatory therapy in UC.