interleukin-8 and Behcet-Syndrome

Behçet's disease (BD) is a systemic inflammatory disorder characterized by recurrent episodes of acute inflammation consisting mainly of neutrophil infiltration around blood vessels in affected tissues. BD probably occurs due to neutrophil-based innate immune responses orchestrated by a complex interplay among gamma-delta T lymphocytes, natural killer T cells, monocytes and Th17 lymphocytes in which type-I interferon is possibly a key element for inflammatory downregulation. However, strong evidence is still scarce. This article compiles the literature in an attempt to summarize the possible mechanisms by which neutrophils are activated in BD and suggests directions for future research.

Topics: Animals; Behcet Syndrome; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interferon Type I; Interleukin-8; Neutrophil Activation; Neutrophils; Th17 Cells; Toll-Like Receptors

Topics: Arthritis, Rheumatoid; Behcet Syndrome; Biomarkers; Bronchitis; Enzyme-Linked Immunosorbent Assay; Humans; Interleukin-10; Interleukin-7; Interleukin-8; Interleukin-9; Lupus Erythematosus, Systemic; Psoriasis; Reagent Kits, Diagnostic; Sjogren's Syndrome

We reported a case of a 22-year old female with a microscopic form of polyarteritis nodosa (PN) who initially manifested Behçet's disease-like symptoms, such as fever, arthralgia, oral aphtha and erythema nodosum, and rapidly progressive glomerulonephritis (RPGN). On admission, her urinalysis showed active nephritic syndrome and her renal function rapidly deteriorated; serum creatinine levels elevated from 1.2 to 3.9 mg/dl within 2 weeks. Skin biopsy specimens from erythema showed panniculitis. Accordingly, she was treated with daily 30 mg of oral prednisolone and three-day intravenous pulse therapy of 1000 mg of methylprednisolone twice. After treatment, skin eruption and oral aphtha disappeared, and the serum creatinine level improved to 1.2 mg/dl. Percutaneous renal biopsy performed on the 28th day showed focal necrotizing glomerulonephritis and hyalinosis of small arteries. Immunofluorescence studies showed only trace stainings for IgG, IgA and beta lc. Electron microscopic findings revealed fusion of the foot process and swelling of endothelial cells, but no dense deposits. Anti-neutrophil cytoplasmic antibody (ANCA) was positive for IgG class with a 40-fold titer by indirect immunofluorescence test and showed a cytoplasmic pattern combined with high urinary IL-8 level (280.1 pg/ml). We diagnosed this case as a microscopic form of PN. ANCA titer and urinary IL-8 correlated positively with the disease activity, and were finally below 8-fold and 58.6 pg/ml, respectively after resolution of RPGN for 42 months. In this case, ANCA was useful not only for differential diagnosis of the patients with systemic vasculitis and crescentic glomerulonephritis, but also for evaluation of the disease activity.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Behcet Syndrome; Disease Progression; Erythema Nodosum; Female; Glomerulonephritis; Humans; Interleukin-8; Polyarteritis Nodosa; Stomatitis, Aphthous

Mucocutaneous type of Behcet's disease (MCBD) is a multisystemic inflammatory disease with oral and genital ulcers with or without skin lesions.. A solid phase, two-site sequential chemiluminescent immunometric assay was used to measure serum levels of interleukin (IL)-6, IL-8 and tumour necrosis factor (TNF)-alpha in 54 normal control subjects and in 64 MCBD patients before and after treatment with levamisole plus colchicine.. We found that 67%, 83% or 67% of MCBD patients had a serum IL-6, IL-8 or TNF-alpha level greater than the upper normal limit of 4.7, 8.7 or 7.4 pg/ml, respectively. The mean serum level of IL-6 (9.9 +/- 2.4 pg/ml, P < 0.005), IL-8 (107.5 +/- 21.4 pg/ml, P < 0.001) or TNF-alpha (22.5 +/- 4.1 pg/ml, P < 0.001) in 64 MCBD patients was significantly higher than that (2.1 +/- 0.2, 5.7 +/- 0.2 or 3.8 +/- 0.2 pg/ml for IL-6, IL-8 or TNF-alpha level, respectively) in normal control subjects. In 43 MCBD patients with all the serum IL-6, IL-8 and TNF-alpha levels higher than their upper normal limits, treatment with levamisole plus colchicine for a period of 0.5-11.5 (mean, 3.2 +/- 2.4) months could significantly reduce the mean serum IL-6, IL-8 and TNF-alpha levels from 9.0 +/- 1.7 to 1.6 +/- 0.2 pg/ml (P < 0.001), 134.6 +/-28.2-6.0 +/- 0.4 pg/ml (P < 0.001) and 25.7 +/- 5.6-3.5 +/- 0.4 pg/ml (P < 0.001), respectively.. Treatment with levamisole and colchicine can result in a significant reduction of serum IL-6, IL-8 or TNF-alpha level in MCBD patients.

Topics: Adjuvants, Immunologic; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Behcet Syndrome; Case-Control Studies; Child; Colchicine; Cytokines; Female; Humans; Interleukin-6; Interleukin-8; Levamisole; Male; Middle Aged; Reference Values; Treatment Outcome; Tumor Necrosis Factor-alpha; Young Adult

To explore the mechanism underlying IL-8-induced neutrophil extracellular trap (NET) formation in patients with ocular-active Behçet's disease (BD) and the effect of inhibiting NET formation on the severity of inflammation in experimental autoimmune uveitis (EAU) mice.. The serum extracellular DNA and neutrophil elastase (NE) and IL-8 levels in patients with ocular-active BD, the expression of myeloperoxidase, NE, and histone H3Cit in IL-8-induced neutrophils isolated from healthy controls, and the effects of NETs on HMC3 cells were detected. Female C57BL/6J mice were immunized with IRBP651-670 to induce EAU and EAU mice received intravitreal injection of the CXCR2 (IL-8 receptor) antagonist SB225002 or PBS. The serum levels of extracellular DNA, NE, and keratinocyte-derived chemokine (the mouse ortholog of human IL-8) and expression of myeloperoxidase, NE, and histone H3Cit in mouse retinas were detected. Disease severity was evaluated by clinical and histopathological scores.. Serum keratinocyte-derived chemokine expression levels in EAU mice and IL-8 expression levels in patients with ocular-active BD increased. IL-8 notably increased NET formation in a dose-dependent manner through an nicotinamide adenine dinucleotide phosphate oxidase and mitogen-activated protein kinase pathway dependent mechanism. IL-8-induced NET formation damaged HMC3 cells in vitro. Pretreatment with SB225002 notably ameliorated the production of NETs in EAU mice.. Our data confirm that NET formation is induced by IL-8. IL-8-induced NET formation was found to be related to mitogen-activated protein kinase and nicotinamide adenine dinucleotide phosphate pathways. Pretreatment with the CXCR2 antagonist SB225002 alleviated neutrophil infiltration and suppressed NET formation in EAU mice.

Topics: Animals; Behcet Syndrome; DNA; Extracellular Traps; Female; Histones; Humans; Interleukin-8; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; NADP; Neutrophils; Peroxidase; Uveitis

Behçet's disease (BD) is a chronic systemic vasculitis with a wide range of clinical findings. It has both autoinflammatory and autoimmune features and manifests with recurrent inflammatory attacks involving the innate immune system. Recently, autoinflammation has started to take place in the pathogenesis of intervertebral disc degeneration. The aim of this study is to evaluate the relationship between intervertebral disc degeneration and BD. We evaluated patients with BD who suffered neck or low back pain in the last 1 year. Eighty four patients underwent musculoskeletal system examination with MRI imaging of the cervical and lumbar vertebrae, and serum levels of IL6, IL8, and TNF-α were determined. The mean age was 47.7 ± 11.5 (range 20-68) years. Cervical and/or lumbar herniation was detected in the MRI imaging of 65 (77.3%) out of 84 patients. The mean IL8 levels of the group with pain and disc herniation and the group with pain and bulging were statistically significantly higher than the other groups (p = 0.007; p = 0.045, respectively). Chronic inflammation in BD may cause disc degeneration and radicular pain to begin and progress earlier in patients.

Topics: Adult; Aged; Behcet Syndrome; Humans; Interleukin-8; Intervertebral Disc Degeneration; Intervertebral Disc Displacement; Low Back Pain; Magnetic Resonance Imaging; Middle Aged; Young Adult

To evaluate the long-term clinical efficacy of apremilast in Behçet's disease (BD) and its effect on serum cytokine levels. This study included 15 BD patients who were treated with apremilast. The rates of change in oral and genital ulcers, skin lesions, arthritis, and arthralgia were evaluated every 3 months for 12 months. The efficacy of apremilast was compared between patients with and without oral ulcer remission. Changes in the serum levels of interferon-gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-10, IL-17A, IL-6, IL-8, and IL-23 between baseline and 3 months after apremilast initiation were compared. After 3 months, oral and genital ulcers disappeared in most cases. The skin and joint lesions tended to improve for up to 6 months; however, recurrence was observed after 9 months. The improvement of genital ulcers was earlier in the oral ulcer remission group than the oral ulcer non-remission group, with the genital ulcers disappearing within the first 3 months. The baseline levels of serum cytokines, analyzed in seven patients, did not exhibit significant associations with specific organ lesions. After administration of apremilast, the TNF-α and IL-23 levels significantly decreased; however, the IFN-γ, IL-6, IL-8, and IL-10 levels did not show significant changes. The rates of decrease in the serum IL-6, IFN-γ, and IL-10 levels were greater in patients with improved oral ulcers. Modulation of serum cytokine levels with apremilast might underlie the efficacy of apremilast in oral ulcers in BD patients.

Topics: Behcet Syndrome; Cytokines; Humans; Interferon-gamma; Interleukin-10; Interleukin-23; Interleukin-6; Interleukin-8; Oral Ulcer; Thalidomide; Tumor Necrosis Factor-alpha

Neutrophil extracellular traps (NETs) are upregulated and promote thrombosis in Behçet's disease (BD). However, whether NETs promote autoinflammation in BD remains unclear. This study aimed to investigate the potential role of NETs in promoting macrophage activation in BD. Firstly, we quantified NETs by measuring double-stranded DNA (dsDNA) using PicoGreen and calculating the proportion of NETosis. Then macrophages were stimulated with BD- or healthy controls (HC)-derived NETs, and IL-8 and TNF-α production and IFN-γ

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Behcet Syndrome; Extracellular Traps; Female; Histones; Humans; Interleukin-8; Macrophage Activation; Macrophages; Male; Middle Aged; Neutrophils; Reactive Oxygen Species; Tumor Necrosis Factor-alpha

This study investigated the levels of interleukin (IL)-8, IL-10, and vascular endothelial growth factor (VEGF) in the aqueous humor (AqH) of patients with Behçet's uveitis (BU) and Fuchs' uveitis syndrome (FUS) during an inactive period and compared these levels with those in the AqH of noninflammatory healthy control subjects.. This prospective and case-control study included 33 patients (16 patients with BU and 17 patients with FUS) and 35 control subjects. IL-8, IL-10, and VEGF levels in the AqH were quantified by performing sandwich enzyme-linked immunosorbent assay. Kruskal-Wallis test was used to compare the cytokine levels in the different groups, and statistical significance was set at p < 0.05.. IL-8 levels were significantly higher in the AqH of patients with BU and FUS than in the AqH of control subjects (p < 0.001 and p < 0.001, respectively). IL-10 levels were significantly lower in the AqH of patients with BU than in the AqH of patients with FUS and of control subjects (p = 0.001 and p < 0.001, respectively). Although VEGF levels were higher in the AqH of patients with FUS than in the AqH of patients with BU and of control subjects, the difference was significant only between patients with FUS and control subjects (p < 0.001).. We observed a significant decrease in IL-10 levels in the AqH of patients with BU and a significant increase in VEGF levels in the AqH of patients with FUS compared to controls. IL-8 and VEGF levels showed no significant difference among uveitis patients.

Topics: Adult; Aqueous Humor; Behcet Syndrome; Biomarkers; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-10; Interleukin-8; Male; Middle Aged; Prospective Studies; Syndrome; Uveitis; Vascular Endothelial Growth Factor A

Behçet's disease is a multisystemic inflammatory disorder as a triad of symptoms including recurrent oral and genital aphthous ulceration and uveitis with unknown pathogenesis. IL-8, a proinflammatory cytokine, has been found increased in the active stage of BD. DNA samples were obtained from 88 patients with BD and 112 healthy control subjects in Denizli province of Turkey. All genotyping experiments of SNPs in IL-8 gene were performed using polymerase chain reaction-restriction fragment polymorphism. We found that IL-8 -845 T > C and -738 T > A sites are non-polymorphic. There were no differences in the polymorphisms of IL-8 +396 G/T, +781 C/T, and +1633 C/T sites except IL-8 -251 T > A in between patients and healthy controls. Analysis of IL-8 polymorphisms indicates that the distribution of frequencies seems to be associated with -251 T > A and gender, -251 T > A and erythema nodosum, -251 T > A and ocular involvement, +781 C > T and erythema nodosum, +396 G > T and pathergy positivity, and +1633 C > T and papulopustular lesion. We demonstrated that the frequencies of IL-8 haplotypes were significantly different with BD patients than control group. We found that the distribution of IL-8 haplotypes was significantly different with genital ulcers, ocular involvement, positive pathergy test, erythema nodosum, papulopustular lesions, and arthritis with BD patients than healthy control individuals. Our study suggests that IL-8 gene polymorphisms may affect susceptibility to BD and increase the risk of developing disease. In order to confirm and assess the association of IL-8 and other cytokine gene polymorphisms in the pathophysiology of BD, large cohort studies are needed.

Topics: Adult; Behcet Syndrome; Cohort Studies; DNA Mutational Analysis; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Interleukin-8; Male; Polymorphism, Single Nucleotide; Risk; Sex Factors; Turkey

Topics: Adult; Behcet Syndrome; Female; Humans; Immune System; Immunoglobulins, Intravenous; Interleukin-8; Longitudinal Studies; Neurosecretory Systems

Complement is involved in many immune-mediated diseases. However, the association of its copy number variations (CNVs) and polymorphisms with Behcet's disease (BD) and Vogt-Koyanagi-Harada syndrome (VKH) is unknown. We examined copy number and mRNA expression by real-time PCR. Cytokine production by stimulated peripheral blood mononuclear cells (PBMCs) in genotyped individuals was measured by ELISA. The frequencies of having more than two copies of C3 were significantly increased in BD and VKH, whereas CNV of C5 was only associated with BD. Increased frequencies of the GG genotype of C3 rs408290 and C5 rs2269067 were found in BD. No association was observed between C3 and C5 SNPs and VKH. mRNA expression in the high CNV group and GG cases of C3 and C5 was significantly higher compared to other genotypes. Increased interleukin-17 and IFN-γ was observed in the high CNV group and GG genotype cases of C3. Interleukin-17 but not IFN-γ was increased in the high CNV group and GG genotype cases of C5. No effect of C3 or C5 genetic variants was seen on the production of TNF-α, IL-10, IL-1β, MCP-1, IL-6 and IL-8. Our study thus provides further evidence for a role of complement in the pathogenesis of uveitis.

Topics: Adult; Asian People; Behcet Syndrome; Complement C3; Complement C5; DNA Copy Number Variations; Female; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Interleukin-10; Interleukin-17; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Male; Middle Aged; Polymorphism, Single Nucleotide; RNA, Messenger; Tumor Necrosis Factor-alpha; Uveomeningoencephalitic Syndrome

Sympathetic storms (SyS) are characterized by hyperactivity of autonomic functions, resulting in episodes of hyperthermia, hypertension, tachycardia, and hyperhidrosis. We show here a patient with neuro-Behçet's disease (NBD) complicated by SyS. Although SyS is well known to occur with brain tumors, trauma, and hydrocephalus, this is the first report to show that SyS is a manifestation of central nervous system involvement in a patient with NBD. High concentrations of norepinephrine (NE) and IL-8 in cerebrospinal fluid reflected the activity of SyS. The patient's symptoms showed almost complete improvement after treatment with corticosteroids and intravenous cyclophosphamide. Also, the concentrations of NE and IL-8 were decreased to normal levels. An awareness of the potential for SyS and adequate immunosuppressant therapy are of importance when dealing with patients with NBD.

Topics: Administration, Oral; Adult; Autonomic Nervous System Diseases; Behcet Syndrome; Cyclophosphamide; Drug Therapy, Combination; Glucocorticoids; Humans; Immunosuppressive Agents; Injections, Intravenous; Interleukin-8; Male; Methylprednisolone; Norepinephrine; Remission Induction

Interleukin (IL)-8 has been shown to correlate with the activity of Behçet's disease (BD). The aim of this study was to develop tools as reliable as IL-8 levels in defining BD severity.. In total, 32 patients with BD and 16 healthy controls were included in the study. Medical history, physical examination, routine laboratory investigations and measurement of serum IL-8 levels were performed. The patients were classified as groups I and II based on the serum IL-8 levels. The patients were then reassigned to groups based on the predictions through discriminating analysis.. In addition to the differences between patient and control groups, the differences between groups I and II, group I and controls, and group II and controls were statistically significant. The discriminating analysis results showed that the patients had been assigned to groups I and II with 100% accuracy.. Discriminating analysis using clinical and routine laboratory findings indicated that 100% of the patients were accurately assigned to the same groups as their IL-8 levels indicated. This suggests that the classification made according to discriminating analysis using these routine variables is a reliable method in determination of the disease severity.

Topics: Adult; Behcet Syndrome; Biomarkers; Discriminant Analysis; Female; Humans; Immunohistochemistry; Interleukin-8; Male; Middle Aged; Prognosis; Severity of Illness Index; Young Adult

Interleukin-8 (IL-8) has been shown previously to associate with different individual clinical manifestations and activity of Behcet's disease (BD), but its association with vascular involvement has not been established.. Forty-five untreated patients with BD and 29 healthy individuals were included in the study. The activity of patients was based on the existence of two or more symptoms and a statistically significantly high Behcet's Disease Activity Index (BDAI) at the time of the study. IL-8, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) results were evaluated with respect to activity, vascular involvement, and other specific individual clinical manifestations of the disease.. IL-8 levels were found to be significantly elevated in active BD compared with inactive BD (P = 0.006) and healthy controls (P = 0.000), with median values of 267 (53-2000), 137 (52-290), and 58 pg/mL (53-160 pg/mL), respectively. Unlike ESR and CRP, IL-8 levels showed a high correlation with BDAI scores (r = 0.743, P = 0.00) and the number of active clinical manifestations (r = 0.646, P = 0.00). Serum levels of IL-8 were increased in patients with oral ulcers, genital ulcers, eye lesions, and vascular lesions, with median values and significance levels of 254.5 (53-2000), P = 0.05; 254.5 (52-1400), P = 0.03; 254.5 (72-2000), P = 0.029; and 593 pg/mL (110-2000 pg/mL), P = 0.001, respectively. In addition, IL-8 levels in the active patient group with vascular involvement were significantly higher than the levels in those without vascular involvement.. Serum IL-8 levels are increased in the active phase of BD. This marker may be useful in the early detection of vascular involvement.

Topics: Adult; Behcet Syndrome; Biomarkers; Blood Sedimentation; C-Reactive Protein; Female; Humans; Interleukin-8; Male; Vasculitis; Venous Thrombosis

Neurological manifestations of Behçet's disease (neuro-Behçet's disease) present in 5-30% of patients. Although cytokines play a pivotal role in pathogenesis of Behçet's disease, published studies about the cerebrospinal fluid (CSF) levels of cytokines in neuro-Behçet's disease are scanty.. Nine patients with active parenchymal, one patient with non-parenchymal neuro-Behçet's disease, six patients with headache attributed to Behçet's disease, 13 patients with viral meningitis, and 19 healthy controls were recruited. Interleukin 6, 8, 10, tumor necrotic factor-alpha, and interferon-gamma were measured in the CSF using enzyme-linked immunosorbent assay method.. Patients with viral meningitis had significantly higher levels of all investigated cytokines except for interferon-gamma in comparison with the patients with parenchymal neuro-Behçet's disease, headache attributed to Behçet's disease and controls (P values <0.05). CSF interleukin 6 was significantly higher in patients with parenchymal neuro-Behçet's disease in comparison with the controls (P=0.025). CSF levels of investigated cytokines had no significant difference between patients with headache attributed to Behçet's disease and controls (P values >0.05). Patients with headache attributed to BD and patients with parenchymal NBD had no significant difference in measured cytokines (P values >0.05).. In contrast to some previous studies, our investigation showed loss of analogy between CSF cytokine profiles of patients with parenchymal neuro-Behçet's disease and viral meningitis. Also we postulated a crucial role for interleukin 6 in immunopathogenesis of neuro-Behçet's disease.

Topics: Adult; Behcet Syndrome; Case-Control Studies; Central Nervous System Diseases; Cytokines; Female; Headache; Humans; Interferon-gamma; Interleukin-10; Interleukin-6; Interleukin-8; Male; Meningitis, Viral; Reference Values; Statistics, Nonparametric; Tumor Necrosis Factor-alpha; Young Adult

To investigate the effect of corticotherapy on IL-8, IL-12, and nitric oxide (NO) production during idiopathic and Behçet active uveitis.. Peripheral venous blood was drawn from 70 patients with active uveitis before and during corticotherapy (32 with Behçet uveitis and 38 with idiopathic uveitis) and from 30 controls. Plasma was collected and peripheral blood mononuclear cells were separated immediately and cultured with or without Concanavaline A. IL-8 and IL-12 levels in plasma and culture supernatants were measured by specific enzyme-linked immunosorbent assay (ELISA). Nitric oxide levels were evaluated using a modified Griess method.. Before therapy, the two groups of patients showed highly significant elevation of IL-8, IL-12, and NO levels compared to control subjects. During therapy, IL-8 and nitric oxide levels were significantly lower in active idiopathic and Behçet active uveitis both in vivo and in vitro. This effect was correlated with therapy duration. In contrast, while significant reduction of IL-12 levels was observed both in vivo and in vitro in idiopathic active uveitis during therapy, this effect was observed in vitro in Behçet active uveitis but not in vivo.. Our results suggest that IL-8, IL-12, and NO are involved in the physiopathological mechanisms of idiopathic and Behçet uveitis. These three molecules showed different degrees of sensitivity to the inhibitory effect of corticoids, reflecting their different regulation by corticotherapy during active phases of the two diseases. According to our study, IL-8 can serve as a marker of inflammatory responses, while IL-12 should be used as a marker of the specific immune responses during active uveitis.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Behcet Syndrome; Female; Humans; Interleukin-12; Interleukin-8; Male; Middle Aged; Nitric Oxide; Uveitis

Topics: Behcet Syndrome; Fas Ligand Protein; Humans; Interleukin-8; Leukemia, Large Granular Lymphocytic; Male; Middle Aged; T-Lymphocytes

During periods of smoking, patients with Behçet's disease have less oral aphthae than in abstinence. To elucidate this observation, human keratinocytes and dermal microvascular endothelial cells (HMEC-1) were incubated with serum of 20 patients with Behçet's disease and 20 healthy controls for 4 hours. Maximum non-toxic concentrations were determined and the cells were further treated with 6 microM nicotine, 3.3% cigarette smoke extract (CES), 100 microM biochanin A, and 6.25/12.5 microM pyrrolidine dithiocarbamate alone and in combinations for 24 hours. Serum IL-8 levels of patients were significantly lower than those of controls. However, after 4 hours incubation with patients' sera, IL-8 release by both cell types was markedly increased when compared with the corresponding serum levels. The levels of IL-6 and vascular endothelial growth factor (VEGF) release were after 4 hours similar with the corresponding levels in serum. IL-1 was not detected. Nicotine significantly decreased IL-8 and -6 release by HMEC-1 maintained in both patients' and controls' sera, but only IL-6 release by keratinocytes maintained in patients' sera. VEGF release by both cells was markedly increased after nicotine treatment in either serum. CES significantly decreased IL-8 release and increased production of VEGF in keratinocytes maintained in patients' serum. The phytoestrogen biochanin A alone and in combination with nicotine further decreased the secretion of IL-8, -6, and VEGF in all experimental settings. Our data support a specific anti-inflammatory effect of nicotine on keratinocytes and endothelial cells maintained in the serum of patients with Behçet's disease. Moreover, biochanin A is likely to exhibit similar and even more profound results than nicotine.

Topics: Adult; Aged; Anti-Inflammatory Agents; Behcet Syndrome; Cell Survival; Endothelial Cells; Female; Genistein; Humans; Interleukin-6; Interleukin-8; Keratinocytes; Male; Middle Aged; Nicotiana; Nicotine; Proline; Smoke; Thiocarbamates; Vascular Endothelial Growth Factor A

Interleukin-8 (IL-8), a CXC chemokine that recruits and activates inflammatory cells, plays a critical role in the pathogenesis of Behcet's disease (BD). To investigate the association of the genetic polymorphism of IL-8 and BD, we genotyped IL-8 -845 T/C, -738 T/A, -353 A/T, -251 A/T, +293 G/T, +678 T/C and receptors CXCR-1 +2607 G/C and CXCR-2 +785 C/T polymorphisms in 119 Korean patients with BD and 119 age- and sex-matched healthy blood donors. Then, single nucleotide polymorphisms (SNPs) and haplotypes were analyzed between patients and controls. There were no SNPs associated with BD. However, the frequency of haplotype TAT inferred from SNPs, IL-8 -353 A/T, -251 A/T and +678 T/C, was significantly higher in patients with BD than controls (5.9 vs 0.0%, P = 0.0001), as was haplotype ATC (6.7 vs 0.0%, P < 0.0001). The haplotype difference was still valid in human leukocyte antigen-B51-negative subjects. In conclusion, we found a significant difference in the distribution of IL-8 gene haplotypes between patients with BD and healthy controls. These results suggest that the genetic polymorphisms of proinflammatory chemokine IL-8 can contribute to the pathogenesis of BD.

Topics: Adult; Behcet Syndrome; Female; Haplotypes; HLA-B Antigens; HLA-B51 Antigen; Humans; Interleukin-8; Korea; Male; Middle Aged; Polymorphism, Single Nucleotide; Receptors, Interleukin-8A; Receptors, Interleukin-8B

Substance P (SP) and calcitonin gene-related peptide (CGRP) are neuropeptides that have a role in several cutaneous diseases and inflammations. Aim. To evaluate SP, CGRP and serum interleukin (IL)-8 levels in Behçet's disease (BD) and to explore the relationship of these peptides with BD activity.. The study group comprised 30 patients with BD, and 30 healthy individuals acted as controls. Serum levels of SP, CGRP and IL-8 were determined by micro-ELISA test during the active and inactive disease periods of patients with BD. These data were compared with each other and controls. Active and inactive periods of BD were established.. The mean +/- SD serum CGRP (ng/ml) and IL-8 levels (pg/ml) in inactive BD (5.87 +/- 2.49 and 0.62 +/- 0.24, respectively) were significantly higher than the control group (4.74 +/- 1.17 and 0.46 +/- 0.11) (P < 0.05 for both). The difference between serum CGRP and IL-8 levels in active BD were also significantly higher than in inactive BD (P < 0.05 for both). Serum SP values (ng/ml) in active BD (18.27 +/- 5.38) were significantly higher than in inactive BD (15.26 +/- 5.74) and controls (12.6 +/- 4.45) (P < 0.05 for all), whereas the difference between the serum SP values in inactive BD and the control group was not statistically significant (P > 0.05).. Serum SP and CGRP may have a role in the pathogenesis of BD. In addition, serum IL-8, SP and CGRP levels can be used as laboratory parameters indicating activity in BD.

Topics: Adult; Behcet Syndrome; Calcitonin Gene-Related Peptide; Female; Humans; Interleukin-8; Male; Prognosis; Substance P

Genetic susceptibility to Behçet's disease (BD) is well documented for HLA-B51; however, contribution of other genetic polymorphisms is estimated to be substantial. Interleukin 8 (IL-8), a potent chemoattractant for neutrophils, has been found to be elevated in BD serum, and the serum concentrations correlate with disease activity. Novel polymorphisms in IL-8 (CXCL8) and in one of its receptors, CXCR2 gene, may have a role in enhanced IL-8 activity in BD.. Three single nucleotide polymorphisms (SNP; -353 A/G, +1530 T/C, +3331 A/G) of the IL-8 gene and 2 SNP (+785 C/T and +1208 T/C) of the CXCR2 gene were screened in 100 patients with BD (61 men, 39 women, mean age 42.1 yrs) and 100 healthy controls (50 men, 50 women, mean age 36.8 yrs) by genotyping with PCR-RFLP and PCR-SSP methods.. No differences were observed between BD patients and controls for the allele and genotype frequencies of the screened IL-8 and CXCR2 gene polymorphisms. Distribution of these polymorphisms revealed no significant differences between clinical subgroups of BD patients. Each pair of the SNP -353/+1530, -353/+3331, and +1530/+3331 of IL-8 and +785/+1208 of CXCR2 showed strong linkage disequilibrium in both patients and controls (p < 0.001 for all). The distribution of the estimated IL-8 and CXCR2 haplotypes revealed no association with BD or any of its clinical subsets.. These results suggest that the IL-8 gene -353 A/G, +1530 T/C, and +3331 A/G and the CXCR2 gene +785 C/T and +1208 T/C polymorphisms have no role in the increased expression of IL-8 in BD.

Topics: Adult; Behcet Syndrome; DNA; Female; Genetic Predisposition to Disease; Genotype; Humans; Interleukin-8; Male; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Receptors, Interleukin-8B

The aim of the present study was to determine synovial levels of ELR (+) CXC chemokines, known to attract mainly neutrophils to inflamed tissues by binding the neutrophil chemokine receptors CXCR1 and CXCR2 and promoting neovascularization in patients with various inflammatory disorders. The study group consisted of 14 patients with Behçet's disease and nine with familial Mediterranean fever. Fourteen patients with rheumatoid arthritis and 16 with osteoarthritis served as controls. Synovial chemokine levels were measured by two-step sandwich enzyme-linked immunosorbent assay, and significant differences were found in the various chemokines studied. In addition to its angiogenic properties, increased synovial levels of interleukin-8 by attraction of more neutrophils to synovial fluids might also be responsible for the acute synovitis in patients with Behçet's disease. However, the absence of chronic changes with the eventual development of pannus and erosions might result from relatively lower expression of interleukin-8 and the transient, short-lived nature of the arthritis observed in these patients.

Topics: Adult; Angiogenesis Inhibitors; Arthritis, Rheumatoid; Behcet Syndrome; Chemokine CXCL1; Chemokine CXCL5; Chemokines, CXC; Familial Mediterranean Fever; Female; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-8; Male; Microtubule-Associated Proteins; Middle Aged; Neovascularization, Pathologic; Osteoarthritis, Knee; Synovial Fluid

Topics: Adult; Behcet Syndrome; Humans; Immunologic Factors; Interferon-alpha; Interleukin-6; Interleukin-8; Male; Treatment Outcome; Tumor Necrosis Factor-alpha

Immune dysregulation has been shown to be one of the major aspects of the yet unknown pathogenesis of Behçet's disease. Interleukin-8 (IL-8), a major chemokine with pivotal effects concerning leukocytes and endothelial cells, has been found to be elevated in patients with Behçet's disease.. To evaluate the significance of elevated levels of IL-8 with respect to the activity of Behçet's disease.. Sixty-seven consecutive patients with Behçet's disease (37 males, 30 females; 32.5 +/- 9.3 years) were enrolled in our study. The number of active clinical manifestations at the time of serum sampling was recorded. The degree of association between disease activity and IL-8, C-reactive protein, and erythrocyte sedimentation rate was assessed.. Serum levels of IL-8 increased as the number of clinically involved organs increased (P < 0.05). C-reactive protein and the erythrocyte sedimentation rate showed no correlation with disease activity.. Our study confirms that the IL-8 level is a more sensitive marker of disease activity than the erythrocyte sedimentation rate and C-reactive protein. It may be assumed that IL-8 plays an important role in the pathophysiology of Behçet's disease.

Topics: Adolescent; Adult; Analysis of Variance; Behcet Syndrome; Biomarkers; Blood Sedimentation; C-Reactive Protein; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Male; Middle Aged

Previous studies of acute generalized exanthematous pustulosis, a peculiar drug hypersensitivity reaction, suggested that CXCL8-producing T cells regulate sterile, polymorphonuclear neutrophil-rich skin inflammations. In this study, we test the hypothesis of whether CXCL8-producing T cells are present in autoinflammatory diseases like pustular psoriasis and Behçet's disease. Immunohistochemistry of normal skin revealed few CD4+ and CD8+ T cells, few CXCL8+ cells, and no neutrophilic infiltration, whereas in acute exacerbations of atopic dermatitis, numerous CD4+ T cells but few CD8+ T cells, neutrophils, or CXCL8+ cells were detected. In contrast, a pronounced infiltration of neutrophils and of predominantly CD4+ T cells was observed in skin biopsies from pustular psoriasis, Behçet's disease, and acute generalized exanthematous pustulosis, with infiltrating T cells strongly positive for CXCL8 and the chemokine receptor CCR6. Skin-derived T cell clones from pustular skin reactions were positive for CCR6 but negative for CCR8 and secreted high amounts of CXCL8 and GM-CSF, often together with IFN-gamma and TNF-alpha after in vitro stimulation. Moreover, some skin-derived T cell clones from Behçet's disease and from pustular psoriasis predominantly produced CXCL8 and GM-CSF, but failed to secrete IL-5 and IFN-gamma. These cells might represent a particular subset as they differ from both Th1 as well as Th2 T cells and are associated with a unique, neutrophil-rich sterile inflammation. Our findings suggest that CXCL8/GM-CSF-producing T cells may orchestrate neutrophil-rich pathologies of chronic autoinflammatory diseases like pustular psoriasis and Behçet's disease.

Topics: Adult; Aged; Behcet Syndrome; CD4 Antigens; CD8 Antigens; Chemokine CCL20; Chemokines, CC; Dermatitis, Atopic; Female; Flow Cytometry; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunohistochemistry; Inflammation; Interferon-gamma; Interleukin-8; Macrophage Inflammatory Proteins; Male; Middle Aged; Neutrophils; Psoriasis; Receptors, CCR6; Receptors, Chemokine; Skin; Skin Diseases; T-Lymphocytes; Tumor Necrosis Factor-alpha

The pathogenesis of Behçet's disease (BD) and polyarteritis nodosa (PAN) is not yet well established. Endothelial cells have been shown to express chemokines that are involved in inflammatory processes. Interleukin-8 (IL-8) is a potent chemoattractant and activator of neutrophils. We evaluated serum IL-8 levels in patients with PAN and BD. We measured serum IL-8 levels in 21 patients with BD and 16 with PAN. Sera from 30 age-matched healthy blood donors were used as normal controls. Serum IL-8 levels were measured by an enzyme-linked immunosorbent assay (ELISA). The mean serum IL-8 level of the active BD (1522.31 pg/ml) and that of the active PAN (654.8 pg/ml) was significantly higher than that of the normal controls (40.39 pg/ml, P <0.05). There was no difference in mean serum IL-8 levels between patients with inactive disease and normal controls. We found higher serum levels of IL-8 in those patients with more severe disease. These results suggest that IL-8 may play a role in the pathogenesis of PAN and/or BD. Our study also suggests a possible relation between serum IL-8 levels and the severity of these diseases.

Topics: Adult; Behcet Syndrome; Female; Humans; Interleukin-8; Male; Middle Aged; Polyarteritis Nodosa; Severity of Illness Index

To investigate whether there are alterations in the humoral immune system in patients with Behçet's disease (BD) with ocular involvement.. Twenty-four BD patients with active uveitis and without any other manifestations of the disease were included in Group I-a. The same patients were reassessed during the convalescence period and assigned to Group I-c. Moreover, 24 age- and sex-matched healthy controls (Group II) were included in the study. Serum levels of immunoglobulin (Ig) A, IgM, complement (C) 3, C4, interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) in Groups I-a, I-c, and II were measured and compared.. IgA, C3, C4, IL-6, IL-8, and TNF-alpha levels were higher in Group I-a than in Groups I-c and II.. IgA-, C3-, C4-, IL6-, IL8-, and TNF-alpha-mediated mechanisms might be responsible for ocular lesions in BD.

Topics: Adult; Antibody Formation; Behcet Syndrome; Complement System Proteins; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulins; Interleukin-6; Interleukin-8; Male; Tumor Necrosis Factor-alpha; Uveitis

Although several immunological abnormalities have been demonstrated in Behçet's disease (BD), the exact mechanism of the inflammatory changes occurring is still unknown. Antigen-presenting cells, such as mononuclear phagocytes, play a major role in the regulation of immune-mediated as well as of non-specific inflammation.. To investigate the serum activity of patients with BD on antigen and chemokine expression of human macrophages in vitro.. Serum of 15 patients (8 women, 7 men; mean age 33 +/- 10 years) with BD was incubated with cultured macrophages isolated from peripheral blood of healthy volunteers. Macrophages maintained in patients' serum, fetal calf serum with/without dexamethasone and interleukin (IL)-4 or gamma-interferon were investigated for alternative macrophage-activation-associated CC-chemokine 1 (AMAC-1) and IL-8 mRNA expression by Northern blotting. In addition, cytocentrifuge macrophage preparations were stained with monoclonal antibodies against proteins indicating alternative (anti-inflammatory) macrophage activation, such as MS-1 high-molecular-weight protein (MS-1-HMWP), RM3/1 antigen (CD163) and 25F9, as well as classical (pro-inflammatory) macrophage activation, such as CD11c, class I receptor binding the Fc part of IgG (FcgammaRI: CD64) and class III receptor binding the Fc part of IgG (FcgammaRIII: CD16).. Macrophages treated with patients' serum showed neither AMAC-1 expression nor staining with monoclonal antibodies for MS-1-HMWP, CD163 or 25F9. Concomitant treatment with IL-4/dexamethasone up-regulated significantly the expression of CD163. In contrast, IL-8 mRNA expression and staining for CD11c and CD64 were strongly positive after treatment with serum of patients with BD. CD64 positivity and IL-8 mRNA expression were more prominent in patients with active BD than in patients with inactive disease.. Taken together, our results indicate that serum of patients with BD induces classical (pro-inflammatory) activation of human peripheral blood macrophages in vitro. Our findings suggest that serum factor(s) may be responsible for inflammatory changes in BD.

Topics: Adult; Behcet Syndrome; Chemokines, CC; Female; Humans; Interleukin-8; Macrophage Activation; Macrophages; Male; Receptors, IgG

Chemokines are a family of chemoattractants of leukocytes that play a critical role for leukocyte recruitment in various inflammatory diseases. The purpose of this study is to investigate the involvement of chemokines, interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in the peripheral blood, with a special reference to disease activities of the patients with Behçet's disease (BD).. The study population consisted of totally 55 patients with BD who had panuveitis (20 patients with active BD, 35 patients with inactive BD) as well as 19 healthy volunteers as control. Disease activity was defined according to the existence of ocular inflammation. IL-8 and MCP-1 concentration levels in the plasma and whole-blood samples were measured by enzyme-linked immunosorbent assay. Whole-blood samples were obtained by lysing cell membranes of peripheral blood cells.. Most of the plasma IL-8 samples were below the detectable limit. Whole-blood IL-8 levels were readily measured. The levels in the patients with active BD were significantly higher than the other two groups. The patients with active and inactive BD showed higher plasma and whole-blood levels of MCP-1 than controls. The plasma and whole-blood MCP-1 levels of the samples collected at the same time showed a linear correlation.. A close relationship was found to exist between the cell-associated IL-8 and the disease activity, while a persistent role of MCP-1 was observed in BD. Measuring the whole-blood levels of chemokines is useful for monitoring the disease activity.

Topics: Adolescent; Adult; Aged; Behcet Syndrome; Chemokine CCL2; Enzyme-Linked Immunosorbent Assay; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Interleukin-8; Male; Middle Aged

This study examined the hypothesis that the polymorphism of Duffy antigen receptor for chemokines (DARC) predisposes to and/or influences the clinical manifestations of Behçet's disease. The serum levels of IL-8 and monocyte chemotactic peptide (MCP)-1, two DARC-binding chemokines, were investigated and related to this polymorphism. Twenty-eight patients with Behçet's disease and 30 healthy blood donors were included in the study. No null phenotypes were found among the patients studied, and the frequencies of the other phenotypes (Fy((a+b-)), Fy((a+b+)), and Fy((a-b+))) did not significantly differ from those found in the blood donor group or reported in the general Caucasian population. No difference was found between the single phenotypes in terms of IL-8 and MCP-1 serum levels, and no relevant association between the clinical characteristics, Behçet's disease-associated human leukocyte antigen (HLA)-B51, and single phenotypes was observed. This investigation indicates that DARC is not a genetic trait significantly associated with or predisposing to Behçet's disease, at least in Caucasian Italians. However, the role of this polymorphism in the development and in the clinical course of the disease awaits further investigation.

Topics: Adult; Antigens, Protozoan; Behcet Syndrome; Chemokine CCL2; Duffy Blood-Group System; Erythrocytes; Female; Genetic Markers; Genetic Predisposition to Disease; Humans; Interleukin-8; Italy; Male; Middle Aged; Phenotype; Polymorphism, Genetic; Protozoan Proteins; Receptors, Cell Surface; Receptors, Chemokine

Behçet's disease (BD) is asystemic immunoinflammatory disorder and the aetiopathogenesis is to be specified. Cytokines play a role in immune response and in many inflammatory diseases. The aim of this case-control study is to investigate serum pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha, interleukin-1beta (IL-1beta), soluble IL-2 receptor (sIL-2R), IL-6, and chemokine IL-8 levels in patients with BD. We also determined the end product of lipid peroxidation (malondialdehyde (MDA)) in BD patients as an index for oxidative stress.. A total of 37 patients (19 men, 18 women) with BD (active, n = 17; inactive, n = 20) and 20 age-matched and sex-matched healthy control subjects (11 men, nine women) included in this cross-sectional, blinded study. Serum TNF-alpha, IL-1beta, sIL-2R, IL-6 and IL-8 levels were determined by a spectrophotometer technique using the immulite chemiluminescent immunometric assay. Lipid peroxidation was evaluated by Wasowicz et aL The levels of cytokines and lipid peroxidation in the active period were compared with the inactive period of the disease. Results are expressed as mean +/- standard error.. IL-1beta levels were below the detection limits of the assay (< 5 pg/ml) in all samples. Mean levels of MDA (8.1+/-0.7 micromol/l), sIL-2R (800+/-38 U/ml), IL-6 (12.6+/-1.1 pg/ml), IL-8 (7.2+/-0.4 pg/ml), and TNF-alpha (7.9+/-0.5 pg/ml) in active BD patients were significantly higher than those in inactive patients (4.3+/-0.5 micromol/l, p < 0.01; 447+/-16 U/ml, p < 0.001; 8.3+/-0.6 pg/ml, p = 0.006; 5.3+/-0.1 pg/ml, p < 0.001; and 5.1 0.2 pg/ml, p < 0.001; respectively) or control subjects (2.1+/-0.2 micromol/l, p < 0.001; 446+/-20 U/ml, p < 0.001; 6.4+/-0.2 pg/ml, p < 0.001; 5.4+/-0.1 pg/ml, p < 0.001; and 4.7+/-0.1 pg/ml, p < 0.001, respectively). On the contrary, only the mean IL-6 level was significantly different between inactive BD and control subjects (p = 0.02). All acute phase reactants were significantly higher in active BD than in inactive period (for each, p < 0.01).. High levels of sIL-2R, IL-6, IL-8 and TNF-alpha indicate the activation of immune system in BD. Serum sIL-2R, IL-6, IL-8 and TNF-alpha seem to be related to disease activity. Increased lipid peroxidation suggests oxidative stress in BD and therefore tissue damage in such patients. Amelioration of clinical manifestations would be envisaged by targeting these cytokines, chemokines and lipid peroxidation with pharmacological agents.

Topics: Adult; Behcet Syndrome; Female; Humans; Interleukin-6; Interleukin-8; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Receptors, Interleukin-2; Tumor Necrosis Factor-alpha

A truncated actin with an N-terminus of Met-44 is known to be selectively increased in neutrophils of patients with Behçet's disease and to be generated proteolytically by PMN-elastase (Yamashita S. et al., Biol. Pharm. Bull., 23, 519-522 (2000); Biol. Pharm. Bull., 24, 119-122 (2001)). In this study, the functions of the N-terminal peptide consisting of Asp-2 to Val-43 of beta-actin (42-merP) and the truncated actin with an N-terminus of Met-44 were examined. We first confirmed that the 42-merP existed in the patient plasma. The motility of human peripheral blood neutrophils and neutrophilic granulocytes differentiated from HL-60 cells was suppressed by the 42-merP. Furthermore, when neutrophil-like cells from HL-60 cells were preincubated with 10 nm 42-merP, migration of the cells induced by chemotactic factors such as fMLP and IL-8 was suppressed. The release of PMN-elastase, which is a neutrophil granular enzyme that is responsible for the production of the 42-merP and truncated actin, was suppressed by pretreating the neutrophils with 42-merP before fMLP-stimulation. The truncated actin was unable to polymerize in 0.1 M KCl, suggesting that the increase of truncated actin damages the reconstitution capacity of actin in neutrophils of the patients. These results suggest that the increase of 42-merP and truncated actin in patients with Behçet's disease changes functions of neutrophils

Topics: Actins; Amino Acid Substitution; Behcet Syndrome; Cell Degranulation; Cell Movement; Cells, Cultured; Chemotaxis, Leukocyte; HL-60 Cells; Humans; In Vitro Techniques; Indicators and Reagents; Interleukin-8; Leukocyte Elastase; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Peptide Fragments

The serum levels of several cytokines were determined in 94 patients with Adamantiades-Behçet's disease (ABD), aged 36.1+/-11.0 years, during the active stage (n = 75) and the inactive stage (n = 19) of the disease. A group of 75 healthy individuals matched for age and sex served as controls. Cytokine levels were determined using commercially available ELISA kits. Of the 75 patients with active disease and 19 with inactive disease, 38 (51%) and 4 (21%), respectively, and 23 healthy controls (31%) were found to have detectable levels of interleukin 8 (IL-8) in their serum (P < 0.05). Also, increased IL-8 serum levels were found in patients with active disease (median 12 pg/ml, P = 0.010) compared to patients with inactive disease (< or = 10 pg/ml) and to healthy controls (< or = 10 pg/ml). In particular, patients with oral aphthous ulcers (n = 51, 34 pg/ml) and neurological features (n = 4, 71 pg/ml) exhibited increased IL-8 levels. In contrast, there was no correlation between disease activity and the serum levels of IL-1alpha, IL-1beta, tumor necrosis factor alpha (TNF-alpha), soluble intercellular adhesion molecule-1 or basic fibroblast growth factor (bFGF). In a second set of experiments, the involvement of dermal microvascular endothelial cells in IL-8 secretion was investigated. Immortalized human dermal microvascular endothelial cells (HMEC-1 cells) were maintained for 4 h in vitro with serum from 18 ABD patients or with IL-1beta, a known stimulator of IL-8 synthesis, TNF-alpha or their combination at five- to tenfold higher concentrations than those found in the serum of ABD patients. Increased IL-8 secretion was found after incubation with ABD patients' serum (median 20 pg/ml), but IL-1beta, TNF-alpha and IL-1beta + TNF-alpha failed to induce IL-8 secretion by HMEC-1 cells (< or = 1-1.2 pg/ml) in biologically relevant concentrations. Our study showed increased IL-8 serum levels in ABD patients with active oral and neurological manifestations. Human microvascular endothelial cells may, at least partially, be responsible for the enhanced IL-8 secretion in the active stage of the disease.

Topics: Acute Disease; Adult; Behcet Syndrome; Blood; Cell Line; Central Nervous System Diseases; Cytokines; Endothelium, Vascular; Female; Fibroblast Growth Factor 2; Humans; Interleukin-8; Male; Middle Aged; Oral Ulcer

Interleukin 8 (IL-8) has recently been under focused investigation because of its possible participation in the evolution of Adamantiades-Behçet's disease.. The reliability of IL-8 as a serological marker for the activity of the disease was investigated in a prospective consecutive trial of 34 cases.. The activity of the disease was clinically evaluated by the number of actively involved organ systems registered on the day of blood sampling and by the presence of oral aphthous ulcers. Serum IL-8 levels were compared to C-reactive protein (CRP) values and the erythrocyte sedimentation rate.. An association of IL-8 levels with the activity of the disease was detected when compared with both the number of active clinical signs (p = 0.024) and the presence of oral aphthous ulcers (p = 0.002). In contrast, no association of CRP and sedimentation rate with the activity of the disease could be detected. A weak correlation of IL-8 levels with sedimentation rate values at 2 h was found (R = 0.37, p = 0.032).. Our results confirm previous data concerning the significance of IL-8 and, in addition, they provide first evidence for the reliability of IL-8 as a serological marker for assessment of the activity of Adamantiades-Behçet's disease in the follow-up of clinical and therapeutic studies.

Topics: Adult; Behcet Syndrome; Biomarkers; Blood Sedimentation; C-Reactive Protein; Female; Humans; Interleukin-8; Male; Reproducibility of Results

Hypersensitivity to a streptococcal antigen is postulated to be the pathogenesis of Behçet's disease. We analyzed T lymphocyte-phenotypes infiltrated in cutaneous pustular lesions in Behçet's disease and found that CD4+ T cells were predominant components although CD8+ T cells were also present in the lesion. In addition, we established T cell lines from pustular lesions of the four patients with a streptococcal antigen, KTH-1. Two of the cell lines showed the cell surface markers of CD8+TCR alpha beta +, and expressed mRNAs for interleukin (IL)-8, tumor necrosis factor (TNF) alpha, and perforin. Two other T cell lines expressed the cell surface markers for CD4+TCR alpha beta +. Cytokine expression pattern of the two CD4+ T cell lines revealed that one is Th1 type and the other is Th2 type. The Th2 type cell line showed marked proliferation with autologous peripheral blood mononuclear cells, suggesting that the self-reactive T cells play some role on the pathogenesis of Behçet's disease.

Topics: Adult; Antigens, Bacterial; Behcet Syndrome; CD4-CD8 Ratio; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Division; Cell Line; Humans; Interleukin-8; Male; Middle Aged; Monocytes; Phenotype; Skin; Streptococcus; T-Lymphocytes; Tumor Necrosis Factor-alpha

Serum interleukin-8 (IL-8) production was measured in 43 Adamantiades-Behçet's disease (A-BD) patients and in 46 healthy volunteers using a sandwich enzyme-linked immunosorbent assay (ELISA). The mean serum IL-8 level of the patients (14.6 +/- 3 pg/ml) was significantly higher than that of controls (10.8 +/- 3 pg/ml, P < 0.05). Since IL-8 is known to have proinflammatory properties, it may play some role in the pathogenesis of A-BD. We also investigated the activity of serum superoxide dismutase (SOD) in the 43 patients with A-BD and in the 46 healthy volunteers. Serum SOD activity was markedly increased in the patients with A-BD (13.1 +/- 3%), especially in active A-BD, compared with that in the healthy volunteers (6.7 +/- 3%, P < 0.01). Our results suggest the involvement of IL-8 and SOD in the pathogenesis of A-BD as seen in other inflammatory diseases.

Topics: Adult; Aged; Behcet Syndrome; Female; Humans; Interleukin-8; Male; Middle Aged; Superoxide Dismutase

To study the in vitro adhesion of polymorphonuclear leucocytes (PMNLs) to endothelial cells in patients with Behçet's disease (BD), and the humoral and cellular factors which may contribute to adhesion.. A total of 118 patients with BD and 60 healthy controls were studied. In vitro adhesion of chromium-51 labelled normal neutrophils to human umbilical vascular endothelial cell (HUVEC) monolayers were studied in the presence of normal serum or serum obtained from patients with BD. Adhesion of neutrophils from patients with BD to HUVEC stimulated with tumour necrosis factor (TNF), interleukin-1 (IL-1), and lipopolysaccharide (LPS) and adhesion molecule (CD11a, CD11b, CD18 and L-selectin) expression on the patient's neutrophils and lymphocytes were determined, and the serum concentration of IL-8 was measured.. Sera from patients with BD were found to enhance the adherence of normal PMNLs to HUVEC monolayers in vitro. Patients' sera induced an increase in surface expression of CD11a and CD18 on normal neutrophils and intercellular adhesion molecule-1 (ICAM-1) expression on HUVECs. The number of CD11a positive neutrophils was greater in the blood of patients with BD than in that of healthy controls (89.4% v 71%; p < 0.001). Pretreatment of HUVECs with IL-1 alpha, TNF alpha or LPS resulted in an increased adhesion of patients' PMNLs greater than that observed for normal PMNLs. Monoclonal antibodies to CD11a, CD11b, CD18, and ICAM-1 caused varying degrees of inhibition of neutrophil adhesion. The concentration of IL-8 was also found to be significantly increased in sera of patients with BD (490 (SD 470) pg/ml) compared with normal controls (97.5 (56.3) pg/ml).. Abnormalities of neutrophils, endothelial cells, or both, have been suggested to be responsible for many of the clinical manifestations of BD. Our findings may explain the underlying mechanism of neutrophil accumulation in Behçet's lesions.

Topics: Antibodies, Monoclonal; Behcet Syndrome; CD11 Antigens; CD18 Antigens; Cell Adhesion; Endothelium, Vascular; Humans; In Vitro Techniques; Intercellular Adhesion Molecule-1; Interleukin-8; Neutrophil Activation; Neutrophils

Topics: Adult; Behcet Syndrome; Female; Humans; Interleukin-8; Male; Middle Aged

The pathogenesis of Behçet's disease (BD) has not yet been determined. Several hypotheses have been postulated and cytokines that control growth proliferation and hematopoiesis of progenitor cells play a role in relation to immune response and inflammatory dysfunction. We investigated whether cytokines play a role in pathogenesis of BD.. We employed the quantitative sandwich enzyme immunoassay technique, in which antibody is already coated on the microtiter plate standard and samples are pipetted into the wells. Antigen present is bound by immobilized antibody. After incubation and washing steps, conjugate, which is enzyme linked polyclonal antibody specific for the antigen is added to the wells. Following a wash to remove any unbound antibody enzyme reagent, a substrate solution is added to the wells, and color develops in proportion to the antigen bound in the initial steps, which can be read in terms of optical density present in the standards and in the samples.. Of a total of 53 samples with BD, 33 (64%) had detectable levels of interleukin 8 (IL-8). Levels of IL-6, tumor necrosis factor alpha and interferon-gamma were not significantly elevated in patients with BD.. We found that IL-8 levels are higher in patients with active BD, and since IL-8 has a potent effect on the neutrophil, this cytokine most likely participates in the inflammatory response of this disease.

Topics: Behcet Syndrome; Humans; Immunoenzyme Techniques; Interferon-gamma; Interleukin-6; Interleukin-8; Tumor Necrosis Factor-alpha

Activated peripheral polymorphonuclear leukocytes (PMNs) and infiltration of PMNs into the lesions are characteristic findings of Behçet's disease (BD). A variety of cytokines, including interleukin 8 (IL-8), have been shown to activate PMNs. To investigate the role of IL-8 in the development of BD lesions, IL-8 production in vivo and in vitro was examined in 25 BD patients. IL-8 levels measured by ELISA in the non stimulated culture supernatants of peripheral mononuclear cells (MNCs) were higher in patients with active BD than in those with inactive BD or normal controls. Without LPS stimulation, IL-8 mRNA expression in incubated MNCs detected by Northern blot analysis was higher in active BD patients than in controls. Polarization assay confirmed the accelerated activity of PMN isolated from patients with active BD. However, these PMNs did not respond to IL-8 as strongly as to FMLP (an exogenous stimulator); a possible reason is that the PMNs of these patients are constantly exposed to IL-8 in vivo. Immunohistochemically, MNCs, endothelial cells and fibroblasts in BD lesions were positively stained by anti-IL-8 antibody. These data indicate that the production of IL-8 may be accelerated in inactive BD and that IL-8 may play an important role in the pathogenesis of BD.

Topics: Adult; Behcet Syndrome; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunohistochemistry; Interleukin-8; Leukocytes, Mononuclear; Male; Middle Aged; Neutrophils; Skin

The etiopathogenesis of Behçet's disease (BD) has not yet been clarified but might involve immune dysfunction. As cytokines are involved in the regulation of immune responses and inflammatory reactions, we investigated whether they may play a role in the pathogenesis of BD.. We investigated spontaneous and lipopolysaccharide (LPS) stimulated production of tumor necrosis factor alpha (TNF alpha), interleukin (IL) 1, IL-6, IL-8 and granulocyte monocyte macrophage colony stimulating factor (GM-CSF) by peripheral blood monocytes from 21 patients with BD, 10 healthy controls and 10 patients with familial Mediterranean fever (FMF), another chronic inflammatory disease. We also studied superoxide generation and surface antigen expression by polymorphonuclear neutrophils (PMN).. The spontaneous secretion of TNF alpha, IL-6 and IL-8 by monocytes was significantly increased in patients with active BD. The secretion of TNF alpha, IL-1, IL-6 and IL-8 was found to be in normal range in asymptomatic patients with FMF. The LPS stimulated production of TNF alpha, IL-6, IL-1 and IL-8 was significantly increased in patients with BD, without any correlation with BD activity. In vitro, PMN spontaneously generated significant amounts of superoxide in patients with active BD.. Taken together, our results suggest that monocyte and PMN dysfunctions may play a role in the pathogenesis of BD.

Topics: Adult; Behcet Syndrome; Complement System Proteins; Cytokines; Familial Mediterranean Fever; Female; Humans; Immunoglobulins; Interleukin-6; Interleukin-8; Male; Middle Aged; Monocytes; Neutrophils; Reference Values; Superoxides; Tumor Necrosis Factor-alpha

The potentiating effect of the soluble factors released from normal or diseased lymphocytes on neutrophil functions were investigated in the presence or absence of mitogens and wall preparations of Streptococcus pyogenes. When normal T lymphocyte populations were stimulated with T cell mitogens or with streptococcal preparations, the supernatants from these cultures potentiated neutrophil chemotaxis, phagocytosis and O2- generation. Upon gel-filtration of these stimulated lymphocyte supernatants, the neutrophil-potentiating activity was inactivated by trypsin or by a 30-min incubation at 130 degrees C, but was not affected by acid treatment at pH 2 or heat treatment at 56 degrees C for 60 min. Its activity was almost not affected by antisera against human interleukin-1, interleukin-2, interferon-gamma or tumour necrosis factor. With the stimulation of T cell mitogens, the supernatants released from the lymphocytes of not only the patients with Behçet's disease but also healthy and diseased controls enhanced neutrophil functions. However, supernatants from streptococcal preparation-stimulated lymphocytes from patients with Behçet's disease had a higher potentiating effect on neutrophil functions. Our study suggests that the enhanced neutrophil functions in patients with Behçet's disease may be related to an abnormally high level of circulating activated T cells in these patients.

Topics: Adult; Behcet Syndrome; Chemotactic Factors; Female; Humans; Interleukin-1; Interleukin-8; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Neutrophils; Peptides; Streptococcus pyogenes