High intracytoplasmatic levels of Il-4 and Il-5 in a patient with Gleichs syndrome: case report

Gleichs syndrome is characterized by recurrent localized angioedema, hypereosinophilia, elevated levels of IgM, rapid weight gain, itchy urticaria and fever. Little is known about the pathogenesis of this disease. Increased serum levels for IL5, IL6 and C5a have been reported before and during clinical exacerbations. In order to better understand the role of the T cells in Gleichs syndrome we analyzed the intracellular cytokine expression in CD3+ cells of a patient affected by the disease. As hypereosinophilia was documented, we asked whether IL-4 and IL-5 levels were increased, and the intracytoplasmatic expression of these Th2-cytokines was determined. The percentage of T lymphocytes (CD3-gated cells) of both CD8- and CD8+ phenotype expressing different cytokines showed an unusually high percentage of Th2-related cytokine (IL-4, IL-5 and IL-13) expressing T lymphocytes. The two new variants (myeloproliferative and lymphoproliferative) seem to account for hypereosinophilia in patients with hypereosinophilic syndrome (HES). In the lymphroliferative variant, the presence of a clonal CD3-CD4+ Th2 like lymphocyte secreting IL-4 and IL-5 in peripheral blood, may explain the hypereosinophilia and the hyper-IgE. In our study we show that the patient had a lymphoproliferative variant and her T cell had a Th2 type phenotype. Moreover, we suggest that Th2 lymphocytes may play a role in the pathogenesis of Gleichs syndrome. Further studies are needed to evaluate the possibility that a polyclonal aspecific activation of Th2 type cells can lead to hypereosinophilia, IgE production and the other manifestations typical of Gleichs syndrome.     

1型糖尿病外周血Th1/Th2细胞因子表达水平的研究

目的检测1型糖尿病患者外周血CD_4~+T细胞分泌细胞因子的水平变化,探讨患者Th1/Th2细胞因子的平衡状态及其在1型糖尿病中的作用。方法对49例1型糖尿病患者和30例健康时照组外周血用刺激物刺激细胞,增加细胞内细胞因子的表达,再加入荧光标记的特异性抗细胞因子单克隆抗体,特异性抗原抗体结合,以流式细胞仪分析特异性细胞因子表达水平。结果1型糖尿病患者Th1型细胞因子干扰素-γ(IFN-γ)、白细胞介素-2(IL-2)表达水平较正常对照组升高,差异有统计学意义(P<0.01)。Th2型细胞因子白细胞介素-4(IL-4)、白细胞介素-10(IL-10)表达水平较正常时照组显著降低,差异有统计学意义(P<0.01)。结论1型糖尿病患者Th1/Th2平衡失调,Th1型反应模式处于优势状态,Th2型反应模式处于弱势状态。Th1/ Th2平衡向Th1方向漂移。     

类风湿关节炎发生发展中TNF-α信号通路与CD4~+T细胞的关系

CD4+T细胞各亚群在类风湿关节炎(RA)的发生发展过程中发挥不同的作用。其中,辅助性T细胞1(Th1)/Th2细胞、Th17/调节性T细胞(Treg)细胞比例的失衡及细胞因子白细胞介素-1(IL-1)、IL-2、干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)等产生的免疫损害,是导致RA慢性炎症的关键因素。TNF-α作为一种重要的促炎细胞因子在RA致病过程中起到了重要作用。TNF-α有两个受体,TNF受体1(TNF receptor 1,TNFR1)在大多数细胞上表达,而TNFR2仅在T细胞等免疫细胞上表达,调节T细胞的存活、活化和增殖。反之,T细胞对TNF-α信号通路也有影响。该文就RA的发病机制中TNF-α及其信号通路和CD4+T细胞各亚群功能的关系加以综述,为RA的防治提供新的思路。     

结肠癌患者外周血Th1/Th2细胞因子的漂移及临床意义

目的检测结肠癌患者外周血CD3T细胞分泌细胞因子的水平变化,分析Thl和Th2细胞的细胞因子免疫活动为肿瘤的免疫治疗提供实验依据。方法首先用刺激物刺激细胞,增加细胞内细胞因子的表达,然后加入荧光标记的特异性抗细胞因子单克隆抗体,特异性抗原抗体结合,最后应用流式细胞仪分析特异性细胞因子表达水平。同时用酶联免疫吸附法ELISA检测相应的细胞因子。结果结肠癌患者Thl型细胞因子干扰素-γ(IFN-γ)、白细胞介素-2(IL-2)、白细胞介素-12(IL-12)表达水平较正常对照组显著降低;Th2型细胞因子白细胞介素-4(IL-4)和白细胞介素-10(IL-10)表达水平较正常对照组升高,差异有显著性意义。肿瘤坏死因子-α(TNF-α)表达水平较正常对照组升高差异有显著性。结论结肠癌患者体内Th2型细胞因子模式占优势状态,这可能是肿瘤细胞发生免疫逃逸,从而导致肿瘤的发生或者转移的一种原因之一。     

Emerging immunological targets in inflammatory bowel disease

Crohn's disease (CD) and ulcerative colitis (UC) are the major forms of inflammatory bowel diseases (IBD) in man. They are caused by damage to the lining of the intestine and deeper layers, due to an excessive immune response directed against components of the gut microflora and poorly controlled by counter-regulatory mechanisms. CD and UC are however immunologically distinct. CD-related inflammation is characterized by a marked mucosal infiltration of T lymphocytes secreting T helper type (Th) 1 and Th17 cytokines. In UC, the local immune response is less polarized but may show enhanced production of IL-5, IL-13 and Th17 cytokines. Downstream however CD and UC share important end-stage effector pathways of intestinal injury, mediated by an active cross-talk between immune and non-immune cells. The clarification of the complex networks of immune-inflammatory mediators operating in the gut of IBD patients has led to the identification of new targets that should facilitate the development of novel biological therapies.     

In vitro immunomodulatory effects of an oleanolic acid-enriched extract of Ligustrum lucidum fruit (Ligustrum lucidum supercritical CO2 extract) on piglet immunocytes

This study was conducted to evaluate the in vitro immunomodulatory effects of supercritical CO₂ Ligustrum lucidum extract (LLE) on the immune cells of piglets. The results showed that the LLE enhanced the proliferative activity of piglet blood lymphocytes and up-regulated the CD4⁺ CD8⁺ and CD4⁺ CD8⁻ cell populations. The LLE also regulated the expression of Th1- and Th2-related cytokines; elevated the levels of IL-2, IFN-γ and TNF-α, which were produced by Th1 lymphocytes; and decreased the levels of IL-4 and IL-10, which were produced by Th2 lymphocytes. Furthermore, the LLE stimulated the NO secretion of lymphocytes. These results indicated that LLE might have potential immunomodulatory effects on the immune system of piglets and provided scientific and experimental foundations for the development of a new kind of LLE immune adjuvant in the pig production.     

Vitamin D Treatment Attenuates Neuroinflammation and Dopaminergic Neurodegeneration in an Animal Model of Parkinson’s Disease,Shifting M1 to M2 Microglia Responses

Microglia-mediated neuroinflammation has been described as a common hallmark of Parkinson’s disease (PD) and is believed to further exacerbate the progressive degeneration of dopaminergic neurons. Current therapies are unable to prevent the disease progression. A significant association has been demonstrated between PD and low levels of vitamin D in patients serum, and vitamin D supplement appears to have a beneficial clinical effect. Herein, we investigated whether vitamin D administered orally in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced preclinical animal model of PD protects against glia-mediated inflammation and nigrostriatal neurodegeneration. Vitamin D significantly attenuated the MPTP-induced loss of tyrosine hydrlase (TH)-positive neuronal cells, microglial cell activation (Iba1-immunoreactive), inducible nitric oxide synthase (iNOS) and TLR-4 expression, typical hallmarks of the pro-inflammatory (M1) activation of microglia. Additionally, Vitamin D was able to decrease pro-inflammatory cytokines mRNA expression in distinct brain areas of the MPTP mouse. Importantly, we also assessed the anti-inflammatory property of vitamin D in the MPTP mouse, in which it upregulated the anti-inflammatory cytokines (IL-10, IL-4 and TGF-β) mRNA expression as well as increasing the expression of CD163, CD206 and CD204, typical hallmarks of alternative activation of microglia for anti-inflammatory signalling (M2). Collectively, these results demonstrate that vitamin D exhibits substantial neuroprotective effects in this PD animal model, by attenuating pro-inflammatory and up-regulating anti-inflammatory processes.     

TACI-Ig induces immune balance of Th cells in MLN via BLyS/APRIL-receptors signaling in rats with adjuvant-induced arthritis

The transmembrane activator and calcium modulator and cyclophilin ligand interactor-immunoglobulin (TACI-Ig), a recombinant fusion protein that modulates B and T cells activation by binding and neutralizing B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), has been shown to have a therapeutic effects on autoimmune disorders. The objective of this study was to investigate immunoregulatory efficacy of TACI-Ig on helper T (Th) cells in mesenteric lymph node (MLN) of adjuvant-induced arthritis (AA) in rats. The levels of BLyS, APRIL, interferon (IFN)-γ, interleukin (IL)-4, transforming growth factor beta (TGF)-β1, and IL-17 were measured by enzyme-linked immunosorbent assay. The localization and expression of TACI, B-cell maturation antigen (BCMA) and B cell activating factor-receptor (BAFF-R) were investigated by immunohistochemistry and western blotting analysis in MLN. Administration of TACI-Ig significantly reduced histological changes, along with decreased Th1 and Th17-cell cytokines and increased CD4⁺CD25⁺FOXP3⁺ regulatory T cell (Treg) and Th2-cell cytokines in MLN of AA rats. The levels of BLyS and APRIL were decreased in MLN homogenate of AA rats after treatment with TACI-Ig. TACI-Ig inhibited TACI and BCMA expression, and increased BAFF-R expression in MLN with AA rats. Taken together, BLyS/APRIL-receptors signaling are important not only for B cell function but for T cell-mediated immune responses. TACI-Ig might exert its anti-inflammatory and immunoregulatory effects through inducing immune balance of Th1/Th2 and Treg/Th17 in peripheral MLN. The mechanisms of TACI-Ig on BLyS/APRIL-receptors-dependent signaling in MLN lymphocytes may play key roles in the pathogenesis of autoimmune disorders.     

Association of cytokine gene polymorphisms and the release of cytokines from peripheral blood mononuclear cells treated with methotrexate and dexamethasone

Immunosuppressive drugs are widely used in the therapy of autoimmune disorders to suppress autoreactive T cells. The immune system is regulated by the release of cytokines. Cytokine are potent immunomodulatory molecules that act as mediators of inflammation and the immune response. Primarily secreted by T cell and macrophages, they influence cellular activation, differentiation, and function. Cytokine production is under genetic control. This is evidenced by the identification of polymorphism in cytokine gene regulatory regions that correlate with intra-individual variations in actual cytokine production. The aim of the study was to examine whether the individual differences in the polymorphic cytokine genes can lead to individual variation in release of cytokines after treatment with methotrexate and glucocorticosteroids. The study was carried out on mononuclear cells isolated from peripheral blood of 72 healthy subjects. The cells were activated with PHA and incubated with increasing concentrations of methotrexate (0.1-10 microM) and dexamethasone (0.01-1 microM). Levels of IL-2, IL-4, IL-6, IL-10, and TNFalpha in the culture supernatants were quantified by flow-cytometry using Th1/Th2 kit and correlated with cytokine gene polymorphisms. The increased concentrations of DEX resulted in comparable cytokine concentrations in cultures from subjects with low and high cytokine genotypes. Despite MTX treatment, the cytokine levels were significantly increased in individuals homozygous for the high producer allele. These results suggest that the cytokine gene variants may influence the efficacy of therapy with some immunosuppressive and anti-inflammatory drugs.     

Cytokine/anti-cytokine therapy – novel treatments for asthma?

Asthma is a chronic inflammatory disease of the airways and there are no preventions or cures. Inflammatory cells through the secretion of cytokines and pro-inflammatory molecules are thought to play a critical role in pathogenesis. Type 2 CD4(+) lymphocytes (Th2 cells) and their cytokines predominate in mild to moderate allergic asthma, whereas severe steroid-resistant asthma has more of a mixed Th2/Th1 phenotype with a Th17 component. Other immune cells, particularly neutrophils, macrophages and dendritic cells, as well structural cells such as epithelial and airway smooth muscle cells also produce disease-associated cytokines in asthma. Increased levels of these immune cells and cytokines have been identified in clinical samples and their potential role in disease demonstrated in studies using mouse models of asthma. Clinical trials with inhibitors of cytokines such as interleukin (IL)-4, -5 and tumour necrosis factor-α have had success in some studies but not others. This may reflect the design of the clinical trials, including treatments regimes and the patient population included in these studies. IL-13, -9 and granulocyte-macrophage colony-stimulating factor are currently being evaluated in clinical trials or preclinically and the outcome of these studies is eagerly awaited. Roles for IL-25, -33, thymic stromal lymphopoietin, interferon-γ, IL-17 and -27 in the regulation of asthma are just emerging, identifying new ways to treat inflammation. Careful interpretation of results from mouse studies will inform the development and application of therapeutic approaches for asthma. The most effective approaches may be combination therapies that suppress multiple cytokines and a range of redundant and disconnected pathways that separately contribute to asthma pathogenesis. Astute application of these approaches may eventually lead to the development of effective asthma therapeutics. Here we review the current state of knowledge in the field.     

卡介菌多糖核酸对生殖器疱疹病人血CD4~+T细胞细胞因子表达影响

目的:研究卡介菌多糖核酸(BCG-PSN)对复发性生殖器疱疹(RGH)病人外周血CD4+T细胞内白细胞介素12(CD4+T-IL-12),干扰素γ(IFN-γ),白细胞介素4(IL-4)表达的影响。方法:用流式细胞仪检测30例经BCG-PSN治疗、15例未予BCG-PSN治疗的RGH病人与15名正常人外周血CD4+T-IL-12,IFN-γ和IL-4表达。结果:治疗前RGH病人外周血CD4+T-IL-12,IFN-γ表达较正常组下降[(1.8±s0.5)%vs(3.3±1.9)%,(3.5±2.6)%vs(5.3±1.5)%;P<0.01],IL-4表达上升[(3.0±0.5)%vs(2.2±0.8)%,P<0.01]。治疗后BCG-PSN组外周血CD4+T-IL-12和IFN-γ水平升高[(3.1±1.6)%vs(1.8±0.5)%,P<0.01;(5.0±2.6)%vs(3.6±2.6)%,P<0.05],IL-4表达下降[(2.4±0.5)%vs(3.0±0.5)%,P<0.01],Th1/Th2恢复正常。结论:RGH病人存在Th1/Th2失衡和IL-12表达低下;BCG-PSN通过诱导外周血CD4+T-IFN-γ,IL-12表达,下调IL-4表达,纠正病人免疫紊乱而提高临床疗效和预防复发。     

An activated set point of T-cell and monocyte inflammatory networks in recent-onset schizophrenia patients involves both pro- and anti-inflammatory forces

We recently described a pro-inflammatory gene expression signature in the monocytes of 60% of patients with recent-onset schizophrenia (SCZ). Here we investigated whether the T-cell system is also in a pro-inflammatory state. A detailed fluorescence-activated cell sorting (FACS) analysis, e.g. of CD3+CD25+ T cells, IFN-γ+, IL-4+, IL-17A+ (CD4+) lymphocytes and CD4+CD25highFoxP3+ regulatory T cells, was performed on peripheral blood of 26 patients with recent-onset SCZ (in 19 of whom the inflammatory gene expression signature of the monocyte had been determined) and in age-/gender-matched healthy controls. Various relevant T-cell cytokines, e.g. sCD25, IFN-γ, IL-17A and IL-4, were measured in serum by a multiplex assay. We detected: (a) not only higher percentages of pro-inflammatory-prone monocytes, activated CD3+CD25+ T cells and pro-inflammatory Th17 cells in patients, but also higher percentages of anti-inflammatory CD4+CD25highFoxP3+ regulatory T cells and IL-4+ lymphocytes; (b) that this activated T-cell set point was reflected in significantly raised serum levels of sCD25; (c) that the up-regulation of IL-4+-containing lymphocytes was predominantly found in patients characterized by a monocyte pro-inflammatory set point; and (d) that regulatory T-cell and Th17-cell numbers were higher in patients irrespective of the pro-inflammatory state of the monocytes. Our data do not support the concept that the T-cell system is in a simple pro-inflammatory state in recent-onset SCZ, but do show that the monocyte and T-cell networks are activated and involve both pro- and anti-inflammatory forces. This suggests control within an activated inflammatory system.     

Tranexamic acid ameliorates rosacea symptoms through regulating immune response and angiogenesis

Rosacea is a chronic inflammatory cutaneous disease characterized by immune system anomalies and vascular hyperreactivity. Recently, therapy of rosacea has improved substantially with the approval of Tranexamic acid (TXA), an antifibrinolytic agent. However, we know little about the underlying mechanism. In this study, we evaluated the effects of TXA and its molecular mechanism on rosacea by using LL37-induced mouse model and HaCaT cell model. Rosacea-like symptoms including skin erythema and histopathological alterations, as well as the elevated pro-inflammatory cytokines (IL-6 and TNFα) and MMP9 expression were significantly ameliorated by TXA treatment. In addition, TXA reduced the expression levels of innate immune gene (TLR2, KLK5 and Camp) and neutrophils relative gene in rosacea-like lesion. For adaptive immune, CD4⁺ T cell infiltration and the gene expression of Th cytokines and chemokines were regulated by TXA in skin lesion. Furthermore, the anti-inflammatory effects of TXA were associated with the inhibition of TLR2, pro-inflammatory cytokines (IL-6 and TNFα) and chemokines (CCL10) expression in LL37-activated HaCaT cells. Finally, TXA repressed the angiogenesis by reducing the number of CD31⁺ cell and downregulating the expression levels of VEGF in rosacea. In conclusion, our finding defines a treatment mechanism by which TXA ameliorates rosacea symptoms by regulating the immune response and angiogenesis.     

Fluoxetine treatment to rats modifies serotonin transporter and cAMP in lymphocytes,CD4+ and CD8+ subpopulations and interleukins 2 and 4

Several lines of evidences indicate that antidepressants produce various immunomodulatory effects. Fluoxetine, an antidepressant and selective serotonin reuptake inhibitor, modulates immune cells in vitro. To explore the in vivo influence of fluoxetine on lymphocytes, male Sprague–Dawley rats were treated daily, 10 mg/kg, or with saline solution for 1, 2 and 3 weeks. The presence of serotonin transporter in CD3+, CD4+ and CD8+ subpopulations of T lymphocytes was determined by immunofluorescence. Serotonin transporter was also labeled with [³H]paroxetine, specific binding defined with imipramine. Plasma levels of pro-inflammatory interleukin 2 (IL-2), and anti-inflammatory interleukin 4 (IL-4), were measured by ELISA; and cAMP concentration by radioimmunoassay. Fluoxetine significantly increased the number of lymphocytes expressing serotonin transporter and elevated the binding of [³H]paroxetine. The percentage of CD4+ cells decreased, that of CD8+ increased, and CD3+ did not change. The ratio CD4+/CD8+ was significantly lowered. Fluoxetine administration elevated the levels of IL-4 at 1, 2 and 3 weeks; and of IL-2, at 2 and 3 weeks. IL-4/IL-2 ratio was significantly increased in fluoxetine group respecting the controls and was similar during the 3 weeks of treatment. Fluoxetine produced a significant decrease in cAMP concentrations in lymphocytes, probably by secondary activation of serotonin receptors. Treatment with fluoxetine modified immune parameters in plasma and lymphocytes of rats, which might be relevant for its systemic therapeutic action as an antidepressant.     

Oral administration of acarbose ameliorates imiquimod-induced psoriasis-like dermatitis in a mouse model

Psoriasis is a chronic autoimmune disease of undefined etiology that involves dysregulated interplay between immune cells and keratinocytes. Acarbose was found to decrease inflammatory parameters in diabetic patients in addition to its anti-diabetic effects. Here, we report that imiquimod (IMQ)-induced epidermal hyperplasia and psoriasis like-inflammation were significantly inhibited by acarbose treatment. Real-time PCR showed that mRNA levels of the cytokines TNF-α, IL-6, IL-1β IL-17A, and IL-22 in skin were also decreased significantly by acarbose. In addition, we found that acarbose reduced infiltration of CD3⁺ T cells and GR-1⁺ neutrophils in lesional skin and also reduced the percentage of IL-17-producing CD4⁺ T cells (Th17) and IL-17- and IL-22-producing γδ T cells in the spleen. In contrast, acarbose increased the frequency of IL-10-producing CD4⁺ regulator Tr1 T cells in the spleen and small intestine. These results indicate that oral administration of acarbose can attenuate the severity of imiquimod-induced psoriasis with local and systemic anti-inflammatory and immune modulation effects, thus suggesting that acarbose is an effective therapeutic strategy for psoriasis regulation.     

Interleukin-21 (IL-21) controls inflammatory pathways in the gut

In both Crohn's disease (CD) and ulcerative colitis (UC), the major forms of inflammatory bowel diseases (IBD) in humans, the pathologic process consists of an aberrant local immune response to components of the bacterial microflora, due to abnormally strong effector cell activity that is poorly controlled by counter-regulatory mechanisms. There is also evidence that mucosal immune cells actively interact with non-immune cells to promote tissue damage, and that cytokines are essential mediators of this cross-talk. Interleukin-21 (IL-21), the latest member of the common gamma-chain-dependent cytokine family, is a product of activated CD4+ T cells and natural killer T cells. IL-21 is produced in excess in CD tissue, where it helps sustain the ongoing Th1 inflammation. High IL-21 production occurs also in the inflamed colon of most patients with UC, a disease that is not associated with a marked Th1 cell response. This suggests that, in the gut, IL-21 can modulate additional inflammatory pathways other than enhancing Th1 cell immunity. Indeed, IL-21 stimulates the secretion of extracellular matrix degrading enzymes by fibroblasts, and of the T cell chemoattractant, MIP-3 alpha, by epithelial cells. These data collectively indicate that IL-21 is a mediator of the chronic inflammatory response in CD and UC, and suggest that IL-21 may be an emerging therapeutic target in IBD.     

H1521, a novel derivative of 4-hydroxyquinoline-3-carboxamide, suppresses the development of lupus in mice by inducing Th1 cytokine profile in T cells

Transferring parental splenocytes into unirradiated F1 mice induces a chronic graft-versus-host disease (GVHD), characterized by the production of Th2 cytokines and immunocomplex-mediated glomerulonephritis resembling systemic lupus erythematosus (SLE). The effects of H1521, a new derivative of 4-hydroxyquinoline-3-carboxamide, were investigated in chronic GVHD lupus model. H1521 was administered to chronic GVHD mice for 10 weeks. Nephritic symptoms were monitored and cytokine expression in the spleen was detected. To clarify the direct effect of H1521 on CD4(+) T cell, CD4(+) T cells were isolated and co-cultured with H1521 under neutral and Th1 or Th2 driving conditions in vitro. H1521 (32 mg/kg) reduced the incidence of proteinuria by 50% in chronic GVHD mice. Ameliorated lupus symptoms and improved renal histopathology damage were also observed. Administration of H1521 had little impact on Th1 cytokine IL-2 and IFN-gamma or Th2 cytokine IL-4 and IL-10 mRNA expression. In contrast, severely deficient IFN-gamma production by concanavalin A-stimulated spleen cells in chronic GVHD mice was completely restored by H1521. In accordance with this, decreased T-bet mRNA expression became normalized with H1521 (32 mg/kg) treatment. In addition, in vitro studies demonstrated that H1521 preferentially favored Th1 differentiation in CD4(+) T cell and promoted IFN-gamma secretion in Th1 differential CD4(+) T cell. However, IL-4 secretion in naive or Th2 differential CD4(+) T cell was unaffected by H1521. In conclusion, H1521 can induce Th1 cytokine profile in CD4(+) T cells and has possible therapeutic value in Th2-predominant immune diseases.     

Analysis of cytokine levels in human lymphangiomas

BACKGROUND: Different theories concerning the origin of lymphangiomas have been formulated but their precise pathogenesis is still unknown. This study aimed to analyze the levels of different cytokines in lymphangioma cyst fluids. MATERIALS AND METHODS: Fluid aspirates from lymphangioma cysts of five patients were obtained. The intracystic levels of interleukin (IL)-6, IL-8, IL-2R and tumor necrosis factor alpha (TNFalpha) were determined in four cases before and one case after OK-432 administration using an immunometric assay. RESULTS: Increased IL-6 levels were observed in all cases. Moreover, elevated IL-2R and TNFalpha levels were observed in three out of four and elevated IL-8 levels in two out of four untreated cases. There was a 25-fold increase in IL-6 after repeated OK-432 injections while IL-8, IL-2R and TNFalpha levels did not change significantly. CONCLUSION: These findings suggest that cytokines may be involved in the pathogenesis of lymphangiomas.     

Effect of diclofenac and antidepressants on the inflammatory response in astrocyte cell culture

Central nervous system (CNS) has a completely separate immune system that communicates with the neurons by small molecules called cytokines. Cytokines are involved in many crucial processes in neuron including cell metabolism and neurotransmitter synthesis. It has been reported that cytokine imbalance is involved in the progression of many CNS diseases such as neuropsychiatric disorders (depression, schizophrenia, autism, and bipolar disorder) and neurodegenerative disorders (Parkinson’s and Alzheimer’s disease). Here, the effects of diclofenac, different antidepressants (sertraline, venlafaxine, and fluvoxamine), and vitamin B₆ (pyridoxine) on IL-10 and tumor necrosis factor-α (TNF-α) change with and without immune challenges with lipopolysaccharide (LPS) were investigated in in vitro culture of astrocytes from 2-day-old Swiss-Albino mice. Diclofenac and Sertraline significantly (p < 0.05) improves anti-inflammatory cytokine (IL-10) while suppress (p < 0.05) LPS-induced elevated level of pro-inflammatory mediators (TNF-α) in astrocyte culture. Pyridoxine was not able to reduce (p > 0.05) TNF-α in the astrocyte culture. Antidepressant (sertraline) showed positive effects (increased IL-10 and reduced TNF-α level) possibly through the suppression of Th1 lymphocytes and monocytes and stimulation of Th2 lymphocytes and monocytes/macrophages. NSAID (diclofenac) showed positive immune regulation effect possibly through the inhibition of cyclo-oxygenase enzyme. Based on these findings, it may conclude that, diclofenac and antidepressants (sertraline) may positively contribute in the cytokine production in astrocyte cell culture.