The present study was carried out in order to investigate the relationship between immune function and the activity of hypothalamic-pituitary-adrenal(HPA) axis in patients with major depression. The subjects were 16 female major depressives and 16 female healthy controls. We measured mitogen-induced production of IL-1 beta, IL-2, IL-6 and serum level of IL-1 beta, IL-2, IL-6 and basal plasma cortisol levels at 8 00 a.m. We measured post-DST(dexamethasone suppression test) cortisol levels in 16 major depressives. The result were as follows : 1) Basal cortisol level was significantly higher in the patients with major depression than in the healthy controls(14.4+/-4.6 microgram/dl, 10.1+/-5.2microgram /dl, respectively, p<0.05). 2) IL-2 production was significantly lower in the patients with major depression than in the healthy controls(1747.3+/-387.9 pg/ml, 2520.2+/-884.1 pg/ml, respectively, p<0.05). There were no significant differences in IL-1 beta and IL-6 production between the patients with major depression and the healthy controls. 3) Serum level of IL-2 was detectable in 12 of 16 patients with major depression and in 10 of 16 healthy controls. There was no significant difference in serum level of IL-2 between two groups. Serum level of IL-1 beta was detectable in 3 of 16 patients with major depression and of 16 healthy controls. We could not detect serum level of IL-6 in both groups. 4) There was significant negative correlation between IL-2 production and post-DST cortisol level(r= -0.89) in the 16 patients with major depression. There was significant negative correlation between serum level of IL-2 and post-DST cortisol level(r= -0.97) in the 12 patients with major depression. There was significant negative correlation between serum level of IL-2 and basal cortisol level(r= -0.65) in the 12 patients with major depression. But there was no significant correlation between IL-2 production and basal cortisol level in the 16 patients with major depression. These findings suggest that immune function is decreased in major depression and the decreased immune function is highly related to the hyperactivity of the HPA axis.
Axis, Cervical Vertebra* ; Depression* ; Female ; Humans ; Hydrocortisone ; Interleukin-1* ; Interleukin-1beta* ; Interleukin-2 ; Interleukin-6 ; Interleukins ; Plasma

BACKGROUND: Atopic dermatitis, a chronic recurrent disease, is frequently encountered in clinical practice. In the last 30 years, the prevalence of atopic dermatitis has rapidly increased due to industrialization. Therefore, there have been attempts in recent years to find new ways of treating and preventing atopic dermatitis. OBJECTIVE: In this double-blind, randomized, placebo-controlled study, a combination of Bifidobacterium bifidum, Lactobacillus acidophilus, Lactobacillus casei, and Lactobacillus salivarius strains were evaluated in the treatment of atopic dermatitis in pediatric patients. METHODS: Forty pediatric patients (23 males and 17 females) aged 1~13 years were enrolled. One eligible individual who was approached declined to participate. The probiotic group was administered a probiotic complex containing B. bifidum, L. acidophilus, L. casei, and L. salivarius for 8 weeks. The placebo group, on the other hand, was administered skim milk powder and dextrose. All of the parameters including serum cytokines, eosinophil cationic protein), SCORing Atopic Dermatitis (SCORAD) index, and total serum immunoglobulin E (IgE) were measured in both the probiotic group and the placebo group at the end of 8 weeks. RESULTS: Probiotic intervention in pediatric atopic dermatitis patients effectively reduced the SCORAD index and serum cytokines interleukin (IL)-5, IL-6, interferon (IFN)-gamma, and total serum IgE levels, but did not reduce levels of serum cytokines IL-2, IL-4, IL-10, ECP, or tumor necrosis factor-alpha (TNF-alpha) compared to the placebo group. CONCLUSION: Our study found probiotics to be effective in reducing atopic dermatitis patients' SCORAD index, serum IL-5, IL-6, IFN-gamma, and total serum IgE levels but not effective in reducing serum IL-2, IL-4, IL-10, ECP, or TNF-alpha levels.
Aged ; Bifidobacterium ; Child ; Cytokines ; Dermatitis, Atopic ; Eosinophils ; Glucose ; Hand ; Humans ; Immunoglobulin E ; Immunoglobulins ; Interferons ; Interleukin-10 ; Interleukin-2 ; Interleukin-4 ; Interleukin-5 ; Interleukin-6 ; Interleukins ; Lactobacillus ; Lactobacillus acidophilus ; Lactobacillus casei ; Male ; Milk ; Prevalence ; Probiotics ; Tumor Necrosis Factor-alpha

Purpose: IL-1 is a multifunctional proinflammatory cytokine. As the proliferative effects of IL-6 and IL-6 receptor expressions on prostatic cancer cells in response to IL-1 have not been determined, the effects of IL-1 on prostatic cancer cell lines were investigated. Materials and Methods: PC-3 and DU-145 cells were cultured in RPMI-1640 medium containing 10% fetal bovine serum. Cell cultures were supplemented with various concentrations of IL-1 (0, 1, 10, 20 and 40ng/ml), and the MMT growth assay performed. PC-3 and DU-145 cells were treated for 2, 4, 8, 12 and 24 h both with and without IL-1. IL-6 and IL-6 receptor (IL-6R) mRNA expressions were investigated using RT-PCR, and the IL-6 levels in cultured supernatant measured by ELISA. Results: The viability of both PC-3 and DU-145 cells decreased after IL-1 treatment (10, 20 and 40ng/mul). With 40ng/ml the IL-1, IL-6 and IL-6RmRNA expressions were lower in PC-3 cells, but unchanged in DU-145 cells, whereas the IL-6 protein production was higher in both PC-3 and DU-145 cells. Conclusions: IL-1 inhibited the proliferation of both PC-3 and DU145 cells. In the PC-3 cells, IL-1 decreased the expressions of IL-6 and IL-6R mRNA, but paradoxically increased the IL-6 production. In the DU-145 cells, IL-1 treatment did not affect the IL-6 or IL-6R mRNA expressions, but the IL-6 production was increased. This discrepancy between IL-1-induced IL-6 mRNA and protein production may be mediated by modification to the protein synthesis or an increased cellular excretion.
Cell Culture Techniques ; Cell Line ; Enzyme-Linked Immunosorbent Assay ; Interleukin-1 ; Interleukin-1beta* ; Interleukin-6* ; Interleukins* ; Prostatic Neoplasms* ; Receptors, Interleukin* ; Receptors, Interleukin-6 ; RNA, Messenger

Cytokines play a pivotal role in maintaining bone homeostasis. Osteoclasts (OCs), the sole bone resorbing cells, are regulated by numerous cytokines. Macrophage colony-stimulating factor and receptor activator of NF-κB ligand play a central role in OC differentiation, which is also termed osteoclastogenesis. Osteoclastogenic cytokines, including tumor necrosis factor-α, IL-1, IL-6, IL-7, IL-8, IL-11, IL-15, IL-17, IL-23, and IL-34, promote OC differentiation, whereas anti-osteoclastogenic cytokines, including interferon (IFN)-α, IFN-β, IFN-γ, IL-3, IL-4, IL-10, IL-12, IL-27, and IL-33, downregulate OC differentiation. Therefore, dynamic regulation of osteoclastogenic and anti-osteoclastogenic cytokines is important in maintaining the balance between bone-resorbing OCs and bone-forming osteoblasts (OBs), which eventually affects bone integrity. This review outlines the osteoclastogenic and anti-osteoclastogenic properties of cytokines with regard to osteoimmunology, and summarizes our current understanding of the roles these cytokines play in osteoclastogenesis.
Cytokines ; Homeostasis ; Interferons ; Interleukin-1 ; Interleukin-10 ; Interleukin-11 ; Interleukin-12 ; Interleukin-15 ; Interleukin-17 ; Interleukin-23 ; Interleukin-27 ; Interleukin-3 ; Interleukin-33 ; Interleukin-4 ; Interleukin-6 ; Interleukin-7 ; Interleukin-8 ; Macrophage Colony-Stimulating Factor ; Necrosis ; Osteoblasts ; Osteoclasts ; RANK Ligand

Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease with various underlying pathophysiologic mechanisms which translate to endotypes, in contrast to clinical phenotypes or histological subtypes. Defining endotypes can help clinicians predict disease prognosis, select subjects suitable for a specific therapy, and assess risks for comorbid conditions, including asthma. Therefore, with recent advancement of biologicals in CRS clinical trials, endotyping can be a breakthrough in treating recalcitrant CRS. CRS is caused by dysregulated immunologic responses to external stimuli, which induce various inflammatory mediators from inflammatory cells, including innate lymphoid cells (ILCs) and T lymphocytes as well as epithelial cells. Thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, and IL-33, which are mainly secreted by epithelial cells in response to external stimuli, act on type 2 ILCs and T helper 2 (Th2) cells, inducing IL-4, IL-5, and IL-13. Local immunoglobulin E (IgE) production is also a signature event in nasal polyps (NP). These inflammatory mediators are novel potential therapeutic targets for recalcitrant CRS. This article reviews recent publications regarding endotypes and endotype-based therapeutic strategies in CRS and NP.
Asthma ; Cytokines ; Epithelial Cells ; Immunoglobulin E ; Immunoglobulins ; Interleukin-13 ; Interleukin-33 ; Interleukin-4 ; Interleukin-5 ; Interleukins ; Lymphocytes ; Nasal Polyps ; Phenotype ; Precision Medicine* ; Prognosis ; T-Lymphocytes

The aim of the present study was to investigate the mRNA expression of several cytokines which were not reported previously from interface tissues around loose cemented acetabulum to obtain better understanding of the biological mechanisms connected with aseptic loosening and osteolysis of THA. We investigated mRNA expression for several cytokines (interleukin-1 alpha [IL-l~a], IL-lp, IL-2, IL-2 receptor[2R], IL-4, IL-5, IL-8, IL-10, transforming growth factor-beta [TGF-p], and interferon- gamma [IFN-y]) by reverse transcription-polymerase chain reaction (RT-PCR) and release of metalloproteinase (MMP)-2 and MMP-9 from the cement-bone interface tissues around five loose polyethylene acetabular components. We did not include TNF-a and IL-6 because the biologic effect of the former is so similar to that of IL-1, and the latter fails to stimulate prostaglandin E, or collagenase production by fibroblsts or synovial cells. Expression of mRNA for IL-1p was detected in four, IL-2R and IL-8 in three, IL-10 and TGF-p in two of five interface tissues .No expression of mRNA for IL-la, IL-2, IL-4, IL-5, and IFN-p was detected. Zymographic analysis for gelatinase/type IV collagenase revealed gelatinolytic bands corresponding to metalloproteinase(MMP)-2 and MMP-9 in cemenl-bone interface tissues. Activated cells phagocytose particles in cement-bone interface tissues expressed more cytokines mRNA than previously known to be related to periprosthetic bone resorption, and secreted metalloproteinases associated with extracellular matrix degradation and fibrosis.
Acetabulum ; Arthroplasty, Replacement, Hip* ; Bone Resorption ; Collagenases ; Cytokines* ; Extracellular Matrix ; Fibrosis ; Interleukin-1 ; Interleukin-10 ; Interleukin-2 ; Interleukin-4 ; Interleukin-5 ; Interleukin-6 ; Interleukin-8 ; Metalloproteases* ; Osteolysis ; Polyethylene ; RNA, Messenger*

PURPOSE: Diverse cytokines influence the pathogenesis of type 1 diabetes mellitus (T1DM) in different ways. We studied the profile of cytokines in sera from type 1 diabetic patients at diagnosis. METHODS: Serum levels of 11 cytokines (IL-1alpha, IL-1beta, IL-1Ra, IL-2, IL-4, IL-6, IL-10, IL-12 (p70), INF-gamma, and TNF-alpha) from 38 newly-diagnosed T1DM patents and 39 healthy controls were measured, using multiplex immunoanalytic xMAP. RESULTS: Patients showed significantly higher levels of IL-1beta (P < 0.01), IL-10 (P < 0.01), and TNF-alpha (P = 0.019), than the healthy controls. In 12 of 35 patients, the insulin autoantibody (IAA) was positive (34%) and the level of IAA was correlated with IL-10 (r = 0.454, P = 0.006), and TNF-alpha (r = 0.368, P = 0.030). CONCLUSION: These results suggest that IL-1beta, TNF-alpha, and IL-10 play a role in the pathogenesis of T1DM, and the level of the IAA is correlated with IL-10 and TNF-alpha.
Autoantibodies ; Cytokines ; Diabetes Mellitus, Type 1 ; Humans ; Insulin ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-10 ; Interleukin-12 ; Interleukin-1beta ; Interleukin-2 ; Interleukin-4 ; Interleukin-6 ; Tumor Necrosis Factor-alpha

BACKGROUND: VitabridC¹² is newly developed and composed of vitamin C and Vitabrid (lamellar, hydrated zinc oxide). OBJECTIVE: In this study, we aimed to investigate the effects of VitabridC¹² on psoriasis and atopic dermatitis. METHODS: Mice with imiquimod-induced psoriasis or Dermatophagoides farinae-induced atopic dermatitis were applied with VitabridC¹². The effects of VitabridC¹² were evaluated by clinical features, histology, and immunologic features by examining cytokines and chemokines. RESULTS: In psoriasis model, VitabridC¹² decreased epidermal thickness and reduced inflammatory cell infiltration. In atopic dermatitis model, VitabridC¹² decreased dermal infiltration of inflammatory cells, epidermal hyperplasia, and hyperkeratosis. VitabridC¹² reduced the expression levels of proinflammatory mediators such as interleukin (IL)-1β, IL-6, IL-8, IL-17A, IL-22, tumor necrosis factor-α, CXCL1, CCL17, and CCL20 as well as COX-2 in imiquimod-induced psoriatic skin lesions. Likewise, VitabridC¹² reduced the expression levels of IL-4, IL-5, IL-13, thymic stromal lymphopoietin, and CCL4 in D. farinae-induced skin lesions, and decreased the serum immunoglobulin E level in the atopic dermatitis mouse model. Particularly, the VitabridC¹²-treated mice showed downregulated expressions of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK), p38, and MAPK/ERK kinase, as well as inhibited phosphorylation of nuclear factor-κB p65. CONCLUSION: Taken together, these findings indicate that VitabridC¹² exhibits anti-inflammatory activities and is a promising candidate as a treatment option for psoriasis or atopic dermatitis.
Animals ; Ascorbic Acid ; Chemokines ; Cytokines ; Dermatitis, Atopic ; Hyperplasia ; Immunoglobulin E ; Immunoglobulins ; Inflammation* ; Interleukin-13 ; Interleukin-17 ; Interleukin-4 ; Interleukin-5 ; Interleukin-6 ; Interleukin-8 ; Interleukins ; Mice ; Necrosis ; Phosphorylation ; Phosphotransferases ; Protein Kinases ; Psoriasis ; Pyroglyphidae ; Skin* ; Zinc

OBJECTIVE: To obtain a global view of lymphocyte subset changes in the peripheral blood and cytokine profile in patients with class IV lupus nephritis (LN). METHODS: A total of 30 patients with biopsy proven active class IV LN, 30 patients with biopsy proven active class V LN, and 30 healthy controls were enrolled. Serum concentration of Th1 cytokines (IFN-γ, IL-1, IL-2, and TNF-α) and Th2 cytokines (IL-4, IL-5, IL-6, IL-10, IL-13) were simultaneously analyzed by Fast Quant Human Th1/Th2 protein array. The expression of lymphocyte subsets was measured by flow cytometer. Clinical parameters such as urine protein of 24 h, autoantibodies and complement were detected. Pearson analysis was used to examine the relation between lymphocyte subsets and clinical parameters, cytokine and clinical parameters. RESULTS: The patients with class IV LN had evident anemia (P<0.001), hypocomplementemia, and hypoalbuminemia (P<0.05). There were no significant difference both in the ratio and number of CD4+ lymphocytes between the controls and the patients. In the patients with class IV LN, the ratio and number of CD4+ lymphocytes were both lower than those of the controls (P<0.01). The ratio and number of CD20+ lymphocytes were both higher than those of the controls (P<0.05), and a significant decrease in CD4+CD25+Foxp3+ regulatory T cells (Tregs) was observed in the patients compared with healthy age-matched controls (P<0.001). The abnormality of lymphocytes in class IV patients was obviously notable, especially in CD4+CD25+Foxp3+ regulatory T cells. In class IV patients, most of the detected cytokines levels were markedly elevated as compared with the controls, including Th2 cytokines INF-γ (P<0.05), IL-2 (P<0.05) and TNF-α (P<0.01), and Th2 cytokines IL-4 (P<0.05), IL-6 (P<0.05), IL-10 (P<0.01) and IL-13 (P<0.01). Only 4 out of 9 cytokines significantly increased in class V patients. In addition to IL-2, all of them belonged to Th2 (IL-4, IL-10 and IL-13) cytokines. There was negative correlation between CD4+CD25+Foxp3+ regulatory cells and urine protein, anti-dsDNA titer or SLEDAI (r=-0.781, -0.746 and -0.646, respectively; P<0.05). There was positive correlation between IL-5 and anti-dsDNA titer (r=0.708, P<0.05), between IL-5 and creatinine (r=0.681, P<0.05), and between IL-10 and SLEDAI (r=0.877, P<0.01). There was also negative correlation between IL-10 and urine protein of 24 h (r=-0.659, P<0.05), between IL-10 and hemoglobin concentration (r=-0.856, P<0.01), and between IL-13 and urine protein of 24 h (r=-0.769, P<0.05). There was little correlation between cytokines and clinical parameters in patients with class V LN. CONCLUSION There is extensive abnormality in lymphocyte subsets and cytokine profile in patients with class IV LN, which may be the mechanism of immunosuppressive agents to treat patients with class IV LN.
Cytokines ; immunology ; Flow Cytometry ; Humans ; Interleukin-1 ; Interleukin-10 ; Interleukin-2 ; Interleukin-4 ; Interleukin-5 ; Interleukin-6 ; Lupus Nephritis ; classification ; immunology ; T-Lymphocytes, Regulatory ; immunology ; Tumor Necrosis Factor-alpha

Interleukin (IL)-17 plays an important role in rhinitis and the level thereof correlates with the severity of disease. However, no mouse model for IL-17-dominant rhinitis has yet been developed. Our objective was to establish a mouse model of IL-17-dominant rhinitis via intranasal application of polyinosinic-polycytidylic acid (abbreviated as Poly(I:C)). Mice were divided into 6 groups (n=8 for each group); 1) 1 negative control group, 2) 1 positive control group (OVA/alum model), 3) 2 Poly(I:C) groups (10 or 100 µg), and 4) 2 OVA/Poly(I:C) groups (10 or 100 µg). The positive control group was treated with the conventional OVA/alum protocol. In the Poly(I:C) and OVA/Poly(I:C) groups, phosphate-buffered saline or an OVA solution plus Poly(I:C) were administered. The OVA/Poly(I:C) groups exhibited significantly greater neutrophil infiltration and increased IL-17/interferon γ expression compared with the other groups. However, the levels of total immunoglobulin E (IgE), OVA-specific IgE, eosinophil infiltration, IL-4, IL-5, IL-6, and IL-10 were significantly lower in the OVA/Poly(I:C) groups than in mice subjected to conventional Th2-dominant OVA/alum treatment (the positive control group). IL-17 and neutrophil measurement, chemokine (C-X-C motif) ligand 1 immunohistochemistry, and confocal microscopy revealed increased numbers of IL-17-secreting cells in the nasal mucosa of the OVA/Poly(I:C) groups, which included natural killer cells, CD4 T cells, and neutrophils. In conclusion, we developed a mouse model of IL-17-dominant rhinitis using OVA together with Poly(I:C). This model will be useful in research on neutrophil- or IL-17-dominant rhinitis.
Animals ; Chemokine CXCL1 ; Eosinophils ; Immunoglobulin E ; Immunoglobulins ; Immunohistochemistry ; Interleukin-10 ; Interleukin-17 ; Interleukin-4 ; Interleukin-5 ; Interleukin-6 ; Interleukins ; Killer Cells, Natural ; Mice* ; Microscopy, Confocal ; Nasal Mucosa ; Neutrophil Infiltration ; Neutrophils ; Ovum ; Poly I-C* ; Rhinitis* ; T-Lymphocytes