The Effect of Jeo Dang‐Tang on Cytokines Production in the Patients with Cerebral Infarction

Abstract

The herbal formulation “Jeo Dang‐Tang” (JDT) has long been used for various cerebrovascular diseases. However, very little has scientific investigation been carried out. The aim of the present study is to investigate the effect of JDT on the production of various cytokines in the patients with cerebral infarction (CI). Peripheral blood mononuclear cells (PBMC) obtained from the patients with CI were cultured for 24 h in the presence or absence of lipopolysaccharide (LPS) or phytohemagglutinin (PHA). The amount of interleukin (IL)‐4, IL‐10 and transforming growth factor (TGF)‐1β, in culture supernatant, was significantly increased in the JDT, LPS or PHA treated cells compared to unstimulated cells (P < 0.05). We also show that increased IL‐4, and IL‐10 level by LPS or PHA was significantly inhibited by JDT in a dose‐dependent manner. Maximal inhibition rate of IL‐4 and IL‐10 production by JDT was 45 ± 2% and 51 ± 5% for LPS‐stimulated cell and 41.5 ± 3% and 70.8 ± 2% for PHA‐stimulated cells, respectively (P < 0.05). On the other hand, JDT significantly increased the LPS or PHA‐induced TGF‐β1 production (P < 0.05). These data suggest that JDT has a regulatory effect on the cytokines production, which might explain its beneficial effect in the treatment of CI.     

The effect of SHJKS on cytokines production and NF-kappaB activation in the peripheral blood mononuclear cells of patients with cerebral infarction

The Korean genuine medicine "Seonghyangjeongkisan" (SHJKS) has long been used for various cerebrovascular diseases. However, very little scientific investigation has been carried out. Cytokines involved in the regulation of inflammatory reactions and immune responses may play a role in the pathogenesis of cerebral infarction (CI). The aim of the present study is to elucidate how SHJKS modulates the inflammatory reaction in lipopolysaccaride (LPS) plus phytohaemagglutinin (PHA)-stimulated peripheral mononuclear cells (PBMCs) from CI patients. The amount of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-8 in PBMC culture supernatant was significantly increased in the LPS plus PHA treated cells compared to unstimulated cells. SHJKS inhibited the TNF-alpha, IL-1beta, IL-6, and IL-8 production in dose dependent manner. Maximal inhibition rate of the TNF-alpha, IL-1beta, IL-6, and IL-8 by SHJGS (1.0 mg/ml) was 68.01 +/- 0.28% (P < 0.01), 52.11 +/- 0.56 % (P < 0.01), 53.42 +/- 0.46 % (P < 0.01), and 46.70 +/- 0.37% (P < 0.05), respectively. In addition, we show that SHJKS suppressed nuclear factor (NF)-kappaB activation induced by LPS plus PHA, leading to suppression of IkappaB-alpha phosphorylation and degradation. These results suggest that SHJKS might have regulatory effects on LPS plus PHA-induced cytokine production and NF-kappaB activation, which might explain its beneficial effect in the treatment of CI.     

Divergence of the inflammatory response in two types of chickens

We compared inflammatory responses to lipopolysaccharide (LPS) injection in laying type (Brown Nick) to broiler type (Avian x Avian) chicks. Rectal temperature was measured at 0, 1, 2, 4, 6, 12, and 24h after LPS injection (0, 0.1, 0.3, 0.6, 1, 2.5, or 5mg/kg bw). In layers, rectal temperature increased from 41.31+/-0.19 degrees C to a maximum 42.27+/-0.41 degrees C at 4h after 1mg/kg LPS. Relative to layers, the febrile response in broilers was considerably lower, delayed in onset, and required higher levels of LPS (5mg/kg). Proliferation of spleen cells from un-injected chicks in response to LPS, PHA, and Con A was evaluated in vitro. IFNgamma, TGFbeta(2), MGF and IL-1beta relative to beta-actin mRNA expression were analyzed in spleen cells stimulated with LPS. Splenocytes from layers had a higher proliferative response to LPS (P=0.045), but lower proliferative response to PHA (P=0.004) and Con A (P=0.004) than broilers. Expression of mRNA for MGF, IL-1beta and IFNgamma was lower in broilers than in layers (P<0.001). Reduced production of the pro-inflammatory cytokines in broilers could have resulted from the observed increased production of the immunosuppressive cytokine TGFbeta(2.) These differences in cytokine expression may explain the blunted febrile response in broilers compared to layers. Because the acute phase response of inflammation causes decreased food intake, the blunted inflammatory response of broilers may permit faster growth.     

The Effect of SHJKS on Cytokines Production and NF-κB Activation in the Peripheral Blood Mononuclear Cells of Patients with Cerebral Infarction

The Korean genuine medicine “Seonghyangjeongkisan” (SHJKS) has long been used for various cerebrovascular diseases. However, very little scientific investigation has been carried out. Cytokines involved in the regulation of inflammatory reactions and immune responses may play a role in the pathogenesis of cerebral infarction (CI). The aim of the present study is to elucidate how SHJKS modulates the inflammatory reaction in lipopolysaccaride (LPS) plus phytohaemagglutinin (PHA)-stimulated peripheral mononuclear cells (PBMCs) from CI patients. The amount of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 in PBMC culture supernatant was significantly increased in the LPS plus PHA treated cells compared to unstimulated cells. SHJKS inhibited the TNF-α, IL-1β, IL-6, and IL-8 production in dose dependent manner. Maximal inhibition rate of the TNF-α, IL-1β, IL-6, and IL-8 by SHJGS (1.0 mg/ml) was 68.01 ± 0.28% (P < 0.01), 52.11 ± 0.56 % (P < 0.01), 53.42 ± 0.46 % (P < 0.01), and 46.70 ± 0.37% (P < 0.05), respectively. In addition, we show that SHJKS suppressed nuclear factor (NF)-κB activation induced by LPS plus PHA, leading to suppression of IκB-α phosphorylation and degradation. These results suggest that SHJKS might have regulatory effects on LPS plus PHA-induced cytokine production and NF-κB activation, which might explain its beneficial effect in the treatment of CI.     

Interleukin-6 production by tumor necrosis factor and lipopolysaccharide-stimulated rat renal cells

Interleukin-6 (IL-6) is produced by various cell types, including monocytes, fibroblasts, and endothelial cells. IL-6 has also been detected in the urine of normal and renal transplant patients. Thus, the possible production of this cytokine by glomeruli and mesangial cells was investigated. Rat glomeruli were obtained by serial sieving of cortical homogenates of blood-free kidneys. Mesangial cells were obtained from the glomeruli and cultured under standard methods in RPMI 1640 medium containing 15% fetal calf serum. Glomeruli or confluent monolayers cells were then incubated in RPMI 1640 for 18 hr, in the presence or not of tumor necrosis factor-alpha (TNF alpha), lipopolysaccharide (LPS), or platelet-activating factor (PAF). IL-6 activity was measured using the IL-6-dependent cell line subclone (B 9-9) and expressed with respect to a standard curve established with recombinant IL-6. Glomeruli generate IL-6 upon TNF alpha (100 ng/ml) and LPS (1 microgram/ml), 11,500 +/- 3000 and 22,000 +/- 7500 U/ml, respectively. Nonstimulated mesangial cells produced 50 +/- 5 U/ml (mean +/- SEM, n = 4) of IL-6. TNF alpha (1 ng/ml) and LPS (1 microgram/ml) induced the production of 800 +/- 90 and 40,000 +/- 5000 U/ml, respectively (n = 4). In contrast, PAF (0.1 nM-1 microM) did not increase IL-6 production from glomeruli or mesangial cells. These results demonstrate that renal cells spontaneously generate minimal amounts of IL-6 and that this production is significantly increased by TNF alpha or LPS. A synergy between LPS and TNF alpha was induced in glomerular cells with 10 ng/ml of TNF alpha and graded concentrations of LPS. Thus, the production of IL-6 by glomerular cells and its modulation by other cytokines or endotoxins may play a role in the local immunological processes leading to immune glomerular diseases.     

Effect of bojungikki-tang on lipopolysaccharide-induced cytokine production from peripheral blood mononuclear cells of chronic fatigue syndrome patients

Bojungikki-tang (BIT) has been widely used to treat patients suffering from chronic fatigue syndrome (CFS). However, its effect has not been yet investigated experimentally. Based upon the clinical presentation of CFS, we hypothesized that cytokines may play a role in the pathogenesis of the disease. We studied the effect of BIT on lipopolysaccharide (LPS)-induced various cytokines production in peripheral blood mononuclear cells (PBMC) of CFS patients. Bojungikki-tang (1 mg/mL) significantly inhibited LPS-induced tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta1 production by 63.55% +/- 0.19%, 55.06% +/- 0.27%, 48.23% +/- 0.48%, 54.09% +/- 0.76%, respectively (P < 0.05). Bojungikki-tang showed a slightly lower inhibitory effect of LPS-induced Interferon (IFN)-gamma production. These results suggest that BIT may be useful in treating fatigue associated with chronic diseases.     

Intracellular production of type I and type II cytokines during HIV-1 progression in Thai patients

A type I to type II cytokine switch on cells of the immune system has been suggested as a critical step in the etiology of HIV infection. In this study, type I and type II cytokine production of both CD4+ and CD8+ T cells activated by superantigen were investigated in 10 healthy donors and 39 HIV-1 infected patients. Patients were divided into 3 groups based on their CD4 count (< 200, 200-500, > 500 cells/microl). Whole blood from each subject was activated by staphylococcal enterotoxin B (SEB) and anti-CD28. Intracellular cytokine stainings for proinflamatory cytokine (TNF-alpha), type I cytokines (IFN-gamma and IL-2) and type II cytokines (IL-4 and IL-5) in CD4+ and CD8+ T lymphocytes were determined by flow cytometer. Type I cytokine (IFN-gamma) expression in CD4+ T cells co-expressing with CD69 were significantly increased in HIV infected patients, particularly in patients with CD4 counts < 200 and 200-500 cells/microl (means +/- S.D. of 20.7 +/- 18.7% and 10.5 +/- 5.9%, respectively) when compared with 4.8 +/- 1.8% in the normal group (p < 0.05). But IL-2 production in both groups of patients was significantly lower than the normal (3.8 +/- 2.6% and 3.2 +/- 1.4% in patients with < 200, 200-500 cells/microl, and 5.9 +/- 1.5% in the normal group) (p < 0.05). For type II cytokines, there was no difference in all groups of subjects when IL-4 was determined. However, IL-5 production was significantly higher in patients with a CD4 count < 200 cells/microl (0.6 +/- 0.5%) than that in the normal group (0.1 +/- 0.1%) (p < 0.005). CD8+ T cells also showed higher IFN-gamma production in patients with a CD4 count < 200 cells/microl (11.9 +/- 4.7%) and 200-500 cells/microl (12.0 +/- 4.3%) than the normal group (5.3 +/- 2.5%) (p < 0.005). In contrast, IL-2 production in CD8+ T cells was low in these HIV infected patients (0.3 +/- 0.2%, 0.3 +/- 0.2%, and 0.3 +/- 0.4% in patients with < 200, 200-500, and > 500 cells/microl, respectively), which was significantly different compared to the control group (1.2 +/- 0.8%) (p < 0.05). For type II cytokines, only IL-4 production in patients with a CD4 count < 200 cells/microl (0.1 +/- 0.1%) was significantly reduced when compared to the other groups (p < 0.05). This study shows that although HIV infection alters the production of both type I and type II cytokines, it does not induce a polarized type I or type II state in the course of HIV-1 progression in Thai patients.     

人脐血多种细胞因子的含量检测及植物血凝素和脂多糖的影响

目的:通过检测人脐血血清多种细胞因子含量,观察植物血凝素(PHA)和脂多糖(LPS)的诱生影响,探讨这些细胞因子的免疫功能及移植物抗宿主病(GVHD)的发病机制。方法:采用双抗体夹心酶联免疫吸附法(ELISA),测定26份正常足月新生儿脐血及16例正常儿童外周血血清中白细胞介素4(IL-4)、IL-10、肿瘤坏死因子α(TNF-α)、γ干扰素(IFN-γ)、IL-12、IL-15、IL-18水平,以及PHA和LPS刺激后单个核细胞分泌上述细胞因子的诱生水平。结果:人脐血血清中IL-4的水平与正常外周血血清水平无显著差异(P＞0.05),脐血血清中IL-12的水平显著高于外周血血清(P＜0.05),其余5种细胞因子脐血血清水平均明显低于正常外周血血清水平(P＜0.05);PHA和LPS刺激后脐血单个核细胞分泌IL-4、IL-10、TNF-α、IFN-γ、IL-12、IL-15和IL-18的水平明显低于正常外周血(P＜0.05),尤以IL-4、TNF-α、IFN-γ、IL-15和IL-18非常明显。结论:脐血血清中上述细胞因子水平普遍低于正常外周血,以及脐血单个核细胞刺激后产生IL-4、IL-10、TNF-α、IFN-γ、IL-12、IL-15和IL-18等细胞因子水平的不足,表明脐血细胞免疫功能不成熟,是脐血移植后GVHD发生率低及程度轻的主要原因之一。     

Tumour necrosis factor production and cell-mediated immunity in anorexia nervosa.

Fourteen patients with anorexia nervosa (AN) were studied for the production of tumour necrosis factor (TNF), the activation of the interferon (IFN) system and cell-mediated cytotoxicity (CMC) and the results were compared with 16 age-matched healthy women. AN patients had significantly increased spontaneous TNF production by peripheral blood mononuclear cells (PBMC) in vitro (16 +/- 5 U/ml versus 4 +/- 3 U/ml in the control group; P less than 0.05), although no TNF was detectable in the plasma from either group. TNF production in vitro, following stimulation of PBMC by phytohaemagglutinin (PHA) or tumour cells, was similar in AN patients and controls; however, lipopolysaccharide (LPS) induced TNF production was found to be lower in AN (P less than 0.1). CMC was significantly lower in AN patients (4 +/- 2 versus 10 +/- 3 in controls, expressed as lytic units/10(6) cells; P less than 0.05), but no difference could be found between AN and controls in IFN activity as reflected by the level of the IFN-induced enzyme 2'-5' oligoadenylate synthetase (2-5A) in PBMC. Beta-endorphins in the plasma were higher in the AN group (P less than 0.05) but these levels could not be correlated to those of IFN, CMC or TNF. Defective CMC and increased TNF production by PBMC in patients with anorexia nervosa may possibly result from the nutritional deficiencies and neuroendocrine abnormalities associated with the disease, and may contribute to the pathophysiology of AN.     

High-level IL-10 production by monoclonal antibody-stimulated human T cells.

We investigated interleukin-10 (IL-10) production in freshly isolated mononuclear cells and purified T cells in response to stimulation with monoclonal antibodies (mAb) recognizing CD3, CD2 and CD28, or with the bacterial products Staphylococcus aureus cells (SAC), staphylococcal enterotoxin (SEA) and lipopolysaccharide (LPS). IL-10 production was compared with that of IL-2, IL-4 and interferon-gamma (IFN-gamma). Similar to the other cytokines, in peripheral blood mononuclear cells (PBMC) from adult donors the highest IL-10 levels were produced in response to CD2 plus CD28 stimulation, within 72-96 hr of stimulation. Levels of IL-10 in response to CD2 plus CD28 stimulation (1.9 +/- 1 ng/ml) exceeded those in response to SEA (0.25 +/- 0.16 ng/ml), SAC (0.43 +/- 0.42 ng/ml), or LPS (0.19 +/- 0.14 ng/ml) stimulation. With adult purified T cells, high levels of IL-10 and IL-4 were measured following CD3 plus CD28 stimulation, and the amounts of both T-helper type-2 (Th2) cytokines decreased following the addition of phorbol myristate acetate (PMA), whereas the synthesis of the Th1 cytokines IL-2 and IFN-gamma was enhanced. When PBMC were stimulated with a CD3 mAb and different other cytokines were added, strong enhancement of IL-10 production was seen upon the addition of IL-2, IL-4, IL-7, IL-12 and IFN-gamma, whereas inhibition was found with transforming growth factor-beta 1 (TGF-beta 1). These data illustrate that in freshly isolated PBMC large amounts of IL-10 can be induced rapidly by appropriate mAb stimulation, and that even in freshly isolated cells IL-4 and IL-10 show signs of parallel regulation.     

IL-1 alpha (-889) promoter polymorphism is a risk factor for osteomyelitis

As osteomyelitis (OM) induces the synthesis of inflammatory cytokines and IL-1 mediates bone resorption by osteoclasts we determined if there is an association between certain common polymorphisms of the genes encoding proinflammatory cytokines (IL-1 alpha and beta, IL-6, TNF-alpha) and OM in adults. The IL-1 alpha (-889) TT genotype was significantly more frequent among 52 OM patients than in 109 healthy controls (13/52, [25.0%] vs. 9/109, [8.3%], P = 0.0081, chi(2) = 7.01, OR = 3.7, 95% CI, 1.35-10.34). Patients who were homozygous for the T allele were younger than the rest of the OM patients (mean age 35.7 +/- 11.5 vs. 58.1 +/- 18.6 years, P = 0.001). IL-1 beta TT (+3953) polymorphism was also more frequent in OM patients (P = 0.014, chi(2) = 5.12, OR = 5.1, 95% CI, 1.21-52.14), but IL-1 beta is in linkage disequilibrium with the IL-1 alpha *T (P < 0.001). Route of infection, chronicity of the infection, type of microorganism isolated, and frequency of relapses were similar in patients with and without the IL-1 alpha TT genotype. There were no associations between OM and polymorphisms of other cytokines genes. IL-1 alpha serum levels were significantly increased in all the OM patients independently of their IL-1 genotype compared to the controls (P = 0.021). Although IL-1 alpha serum levels were not significantly higher in patients with the IL-1 alpha (-889) polymorphism, this does not exclude a difference in production of IL-1 alpha by osteoclasts or other inflammatory cells at the site of infection.     

Peripheral blood CD4+ and CD8+ T cell type 1 and type 2 cytokine production in atopic asthmatic and normal subjects

BACKGROUND: Increased production of IL-4 and IL-5 and decreased production of IFN-gamma by CD4+ T cells has been implicated in asthma pathogenesis. However, CD8+ T cells also produce type 1 and type 2 cytokines and the relative roles of CD4+ and CD8+ T cell cytokine production in asthma have not been previously studied. OBJECTIVE: To determine the production of the type 1 and type 2 cytokines by CD4+ and CD8+ T cell subsets in asthmatic and normal subjects. METHODS: Intracellular cytokine staining for IL-4, -5, -10, -13 and IFN-gamma was analysed in peripheral blood CD4+ and CD8+ T cells from 24 atopic asthmatic and 20 normal subjects. RESULTS: Both subsets of T cells produced all cytokines studied and there were no significant differences between CD4+ and CD8+ T cells in their capacity to produce either type 1 or type 2 cytokines. There were significantly increased frequencies of IFN-gamma-positive CD4+ (13.1 +/- 2.4%, vs. 7.3 +/- 1.4%) and CD8+ (20.0 +/- 2.9%, vs. 9.6 +/- 2.1%) T cells in asthmatic subjects compared with normal subjects (P < 0.05), but not in frequencies of CD4+ or CD8+ T cells staining positively for IL-4, -5, -10 or -13. CONCLUSION: The frequencies of peripheral blood CD8+ T cells producing type 1 and type 2 cytokines are comparable with the frequencies of CD4+ T cells. There was an increased frequency of IFN-gamma producing CD4+ and CD8+ T cells in asthmatic compared with normal subjects. Further studies investigating T cells derived from the airways and investigating various stages within the disease process are required to further elucidate the importance of type 2 and type 1 T cell cytokine production in the pathogenesis of human allergic disease.     

Enhancing of anti-viral activity against HIV-1 by stimulation of CD8+ T cells with thymic peptides.

HIV-1 can be neutralized by soluble factors produced and secreted by activated CD8+ T cells. Production of such anti-viral CD8 factors (including chemokines) can be induced with IL-2 or phytohaemagglutinin (PHA). In addition to PHA or IL-2, we have co-stimulated CD8+ T cells with PHA/IL-2 and a mixture of thymic peptides (TP) of molecular weights below 10 kD. For the activation, CD8+ T cells were purified from peripheral blood mononuclear cells of HIV-1- individuals and any resultant anti-viral activity was monitored using an HIV-1 neutralization assay. Using HIV-1 isolates highly resistant to chemokine inhibition we detected significantly higher levels of HIV-1 neutralizing activity in CD8+ T cell culture supernatants which had been co-activated with TP. When the TP-induced anti-viral activity was monitored, neutralization of both non-syncytia-inducing (NSI) and syncytia-inducing (SI) patient isolates was enhanced by 38% (NSI, PHA +/- TP), 66% (SI, PHA +/- TP), 28% (NSI, IL-2 +/- TP), and 57% (SI, IL-2 +/- TP) compared with the anti-viral activity present in supernatants from CD8+ T cell cultures stimulated only with PHA or IL-2. Peptide sequence analysis of purified TP showed that the TP mixture predominantly contains peptides with homology to human histone and collagen sequences. Our data demonstrate that CD8+ T cells are additionally activated by a mixture of TP. In this way, the production of HIV-1 neutralizing CD8 factors can be enhanced.     

Passive immunization against tumour necrosis factor-alpha (TNF-alpha) and IL-1 beta protects from LPS enhancing glomerular injury in nephrotoxic nephritis in rats.

Glomerular injury caused by injection of heterologous anti-glomerular basement membrane antibodies (anti-GBM Ab) is increased in rats pretreated with small doses of bacterial lipopolysaccharide (LPS). We have investigated the involvement of tumour necrosis factor-alpha (TNF-alpha), IL-1 alpha and IL-1 beta in this phenomenon by passive immunization against these cytokines. Anti-TNF-alpha or anti-IL-1 beta antibodies given 1.5 h before the induction of nephritis significantly decreased injury in this model, whether assessed by the magnitude of albuminuria, the prevalence of glomerular capillary thrombi or the intensity of glomerular neutrophil infiltrate. Albuminuria in anti-GBM Ab alone was 11 +/- 3, LPS/anti-GBM Ab 87 +/- 22, and anti-TNF-alpha antibodies/LPS/anti-GBM Ab 21 +/- 6 mg/24 h (mean +/- s.e.) P < 0.05. Passive immunization with antibodies to IL-1 beta had a similar effect (anti-GBM Ab, 0.6 +/- 0.1, LPS/anti-GBM Ab, 92 +/- 19, anti-IL-1 beta antibodies/LPS/anti-GBM Ab 39 +/- 8 mg/24 h, P < 0.05). The prevalence of glomerular capillary thrombi was also reduced significantly by these treatments; from 22 +/- 5% to 4 +/- 1% in the case of anti-TNF-alpha antibodies and 28 +/- 5% to 13 +/- 4% with anti-IL-1 beta antibodies. Similarly, the glomerular neutrophil infiltrate was also reduced by these treatments; from 42 +/- 3 to 25 +/- 1 in the case of anti-TNF-alpha and 47 +/- 2 to 30 +/- 1 with anti-IL-1 beta antibodies. In contrast, passive immunization against IL-1 alpha had no effect on either albumin excretion (4 +/- 3, 83 +/- 22 and 77 +/- 24 mg/24 h), glomerular capillary thrombi (2 +/- 1; 19 +/- 5 and 16 +/- 3) or glomerular neutrophil infiltrate (22 +/- 3; 47 +/- 5 and 48 +/- 5 from the three groups respectively). These results demonstrate that enhanced antibody mediated injury in the kidney is modulated by TNF-alpha and IL-1 beta but not by IL-1 alpha.     

The in vitro immunosuppressive effects of moclobemide in healthy volunteers

BACKGROUND: Many studies have demonstrated that major depression is related to an activation of the inflammatory response system (IRS) with an increased production of proinflammatory cytokines. It has been shown that tricyclic antidepressants and serotonin reuptake inhibitors suppress the activation of the IRS in depression and have negative immunoregulatory effects in vitro. Little is known on the immune effects of moclobemide, a reversible monoamine oxidase A inhibitor. METHODS: We examined, in nine normal volunteers, the in vitro effects of moclobemide on the production of interleukin-6 (IL-6), IL-8, tumor necrosis factor-alpha (TNFalpha), interferon-gamma (IFNgamma), IL-10 and the IL-1 receptor antagonist (IL-1RA) by diluted whole blood stimulated or not with lipopolysaccharide (LPS)+phytohemagglutinin (PHA). RESULTS: Moclobemide 10(-3) and 10(-5) M significantly suppressed the unstimulated production of TNFalpha and IL-8, and significantly enhanced the stimulated-production of IL-10. The production of IL-6, IL-1RA and IFNgamma was not significantly affected either in the unstimulated or stimulated conditions. CONCLUSIONS: Moclobemide has negative immunoregulatory capacities through inhibition of the production of proinflammatory cytokines, i.e. TNFalpha and IL-8, and through enhancement of the production of IL-10, an anti-inflammatory cytokine.     

Circulating antiinflammatory cytokine IL-10 in patients with inflammatory bowel disease (IBD).

IBD is characterized by increased serum concentrations of different cytokines. IL-10 inhibits the production of proinflammatory cytokines such as IL-1, tumour necrosis factor-alpha (TNF-a), interferon-gamma (IFN-gamma) and IL-6 through inhibitory action on Th1 cells and macrophages, and it is thought to be a suppressor type cytokine. In the present study we determined serum concentrations of IL-10 in patients with ulcerative colitis (UC) and Crohn's disease (CD). We measured human IL-10 by our own newly established ELISA system using PharMingen antibodies. Serum antibodies were assessed in 44 patients with UC, 40 patients with CD, and in 30 healthy controls. Human IL-10 serum levels were significantly increased in patients with active UC (144 +/- 34 pg/ml (mean +/- s.e.m.), P < 0.001) and in active CD (132 +/- 32 pg/ml, P < 0.001) compared with healthy controls (44 +/- 9.5 pg/ml). Only patients with active CD and active UC presented with significantly increased IL-10 serum levels, while patients with inactive disease did not show any significant increase. There was no statistically significant difference between IL-10 serum levels in patients with CD or UC. Compared with clinical disease activity indices there was a significant correlation between IL-10 serum concentration and CDAI in patients with CD (r = 0.45, P < 0.01) and CAI in UC patients (r = 0.39, P < 0.05). Comparing IL-10 serum levels with serum concentrations of other proinflammatory cytokines there was a significant correlation to serum levels of sIL-2R (r = 0.417, P < 0.05) and IL-6 (r = 0.387, P < 0.05) in patients with CD. Serum cytokine levels in patients with UC did not show any significant correlation to IL-10 serum concentration. IL-10 is elevated in serum of patients with active CD and UC, suggesting that IL-10 acts as a naturally occurring damper in the acute inflammatory process of IBD.     

Effect of Danchunwhangagam on LPS or DFX-Induced Cytokine Production in Peripheral Mononuclear Cells of Cerebral Infarction Patients

The Danchunwhangagam (DCWGG) has long been used for various cerebrovascular diseases. However, little scientific investigation has been carried out. Cytokines involved in the regulation of inflammatory reactions and immune responses may play a role in the pathogenesis of cerebral infarction (CI). The aim of the present study is to investigate the effect of DCWGG on the production of proinflammatory cytokines in peripheral blood mononuclear cells (PBMCs) from CI patients. The amount of tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1β, IL-6, and IL-8 in PBMC culture supernatant was significantly increased in the lipopolysaccaride (LPS)- or desferrioxamine (DFX)-treated cells compared with unstimulated cells. We showed that DCWGG inhibited the production of TNF-α, IL-1α, IL-1β IL-6, and IL-8 induced by LPS in a dose-dependent manner. Also, DCWGG inhibited TNF-α, IL-1α, IL-β, IL-6, and IL-8 production-induced DFX in dose-dependent manner. These results suggest that DCWGG might have regulatory effects on LPS- or DFX-induced cytokine production, which might explain its beneficial effect in the treatment of CI.     

Effect of Danchunwhangagam on LPS or DFX-induced cytokine production in peripheral mononuclear cells of cerebral infarction patients

The Danchunwhangagam (DCWGG) has long been used for various cerebrovascular diseases. However, little scientific investigation has been carried out. Cytokines involved in the regulation of inflammatory reactions and immune responses may play a role in the pathogenesis of cerebral infarction (CI). The aim of the present study is to investigate the effect of DCWGG on the production of proinflammatory cytokines in peripheral blood mononuclear cells (PBMCs) from CI patients. The amount of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, IL-1beta, IL-6, and IL-8 in PBMC culture supernatant was significantly increased in the lipopolysaccaride (LPS)- or desferrioxamine (DFX)-treated cells compared with unstimulated cells. We showed that DCWGG inhibited the production of TNF-alpha, IL-1alpha, IL-1beta IL-6, and IL-8 induced by LPS in a dose-dependent manner. Also, DCWGG inhibited TNF-alpha, IL-1alpha, IL-beta, IL-6, and IL-8 production-induced DFX in dose-dependent manner. These results suggest that DCWGG might have regulatory effects on LPS- or DFX-induced cytokine production, which might explain its beneficial effect in the treatment of CI.