• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.175-184
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• 1999

Background: Bronchial asthma is characterized by chronic eosinophilic inflammatory airway disease associated with bronchial hyperresponsiveness and reversible airway obstruction. Bronchial inflammation in asthma may depend in part on the activation of T helper lymphocytes that elaborate proinflammatory cytokines. T helper (Th) lymphocytes can be divided into two categories; Th1 lymphocytes, which secrete IL-2, IL-12 and IFN-$\gamma$, and Th2 lymphocytes, which secrete IL-4, IL-5, IL-6 and IL-10. Th2 lymphocytes appear to induce allergic responses, whereas Th1 lymphocytes induce delayed-type hypersensitivity response. Some infections, such as tuberculosis, cultivate a Th1 immunological environment and inhibit Th2 lymphocytes function. The presence of such infections might inhibit Th2 immune responses and thus protect development of atopic diseases. Method: 15 patients with allergic bronchial asthma, 10 patients with intrinsic bronchial asthma, and 10 healthy volunteers were studied. The serum concentrations of IFN-$\gamma$, IL-12, IL-4, IL-5, and IL-10 were measured by ELISA method and tuberculin skin test was estimated in different groups. Results: The positive response rates of tuberculin test were 46.7% in patients with allergic asthma, 100% in patients with intrinsic asthma and 60% in normal controls. The positive response rates were significantly lower in patients with allergic asthma than those of in patients with intrinsic asthma (p<0.05). Degree of responses to tuberculin test were $12.0{\pm}9.6mm$ in patients with allergic asthma, $18.4{\pm}4.5mm$ in patients with intrinsic asthma and $10.9{\pm}8.8mm$ in normal controls. The degree of responses were significantly reduced in patients with allergic asthma than those of patients with intrinsic asthma (p<0.05). The serum levels of IL-5 in patients with allergic asthma were significantly higher than in patients with intrinsic asthma and normal controls (p<0.05), although it was insignificant. the serum levels of IL-4 and IL-10 in patients with allergic asthma were higher than that of intrinsic asthma and normal controls. The serum levels of IL-12 and IFN-$\gamma$ in patients with allergic asthma and intrinsic asthma were significantly lower than those in normal controls(p<0.05). The serum levels of total immunoglobulin E (IgE) and peripheral blood eosinophile counts in patients with allergic asthma were significantly higher than those in normal controls. Peripheral blood esinophil counts had a significant correlation with the serum levels of total IgE, IL-5 and IL-10 in patients with allergic asthma (p<0.05). Conclusion: These results have showed that Th1 lymphocyte functions were lowered and Th2 lymphocyte functions were elevated in patients with allergic asthma than those in normal controls. Suppression of Th1 lymphocyte functions by activation of Th2 lymphocyte might be one of the important aspects of pathogenesis in allergic bronchial asthma.

• Food Science and Biotechnology
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• v.17 no.3
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• pp.631-636
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• 2008

Acanthopanax divaricatus var. albeofructus (ADA) have been shown to have various levels of activity such as antioxidant, anticancer, antivirus, and immunostimulatory effects. However, little is known about its mechanism related to the modulation of immune activities. In this study, a water extract of ADA leaves were used to treat human peripheral blood mononuclear cells (hPBMC) to determine the underlying mechanisms for the immunostimulatory effects. To characterize its immunomodulatory activity, the secretion level of various cytokines including IL-2, IL-4, IL-6, IL-10, IL-12, IFN-$\gamma$, and TNF-$\alpha$ were measured using enzyme-linked immunosorbent assay (ELISA). Treatment of hPBMC with ADA leaf extract in an in vitro experiment induced various Th1 cytokines in a dose-dependent manner. A significant increase of IL-2, IL-12, IFN-$\gamma$, and TNF-$\alpha$ secretion was observed in the presence of ADA leaf extract. In contrast, Th2 cytokines including IL-4 and IL-6 were suppressed. There was no significant change in IL-10 release. Our results showed an increase in Th1 and a decrease in Th2 cytokine secretion which suggests that ADA may influence the immune response towards a predominance of Th1 cytokines in the immune system.

• Tuberculosis and Respiratory Diseases
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• v.56 no.1
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• pp.51-66
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• 2004

Objectives : The matrix metalloproteinases (MMPs) that participate in the extracellular matrix metabolism play a important role in the progression of pulmonary fibrosis. The effects of the MMPs are regulated by several factors including Th-1 cytokines, $interferon-{\gamma}$ ($IFN-{\gamma}$). Up to now, $IFN-{\gamma}$ is known to inhibit pulmonary fibrosis, but little is known regarding the exact effect of $IFN-{\gamma}$ on the regulation of the MMPs. This study investigated the effects of $interferon-{\gamma}$ on the pulmonary fibrosis and the expression of the lung MMP-2,-9, TIMP-1,-2, and Th-2 cytokines in aa rat model of bleomycin induced pulmonary fibrosis. Materials and methods : Male, specific pathogen-free Sprague-Dawley rats were subjected to an intratracheal bleomycin instillation. The rats were randomized to a saline control, a bleomycin treated, and a bleomycin+$IFN-{\gamma}$ treated group. The bleomycin+$IFN-{\gamma}$ treated group was subjected to an intramuscular injection of $IFN-{\gamma}$ for 14 days. At 3, 7, 14, and 28 days after the bleomycin instillation, the rats were sacrificed and the lungs were harvested. In order to evaluate the effects of the $IFN-{\gamma}$ on lung fibrosis and inflammation, the lung hydroxyproline content, inflammation and fibrosis score were measured. Western blotting, zymography and reverse zymography were performed at 3, 7, 14, 28 days after bleomycin instillation in order to evaluate the MMP-2,-9, and TIMP-1,-2 expression level. ELISA was performed to determine the IL-4 and IL-13 level in a lung homogenate. Results : 1. 7 days after bleomycin instillation, inflammatory changes were more severe in the bleomycin+$IFN-{\gamma}$ group than the bleomycin group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$2.08{\pm}0.15:2.74{\pm}0.29$, P<0.05), but 28 days after bleomycin instillation, lung fibrosis was significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$3.94{\pm}0.43:2.64{\pm}0.13$, P<0.05). 2. 28 days after bleomycin instillation, the lung hydroxyproline content was significantly reduced as a result of $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$294.04{\pm}31.73{\mu}g/g:194.92{\pm}15.51{\mu}g/g$, P<0.05). 3. Western blotting showed that the MMP-2 level was increased as a result of the bleomycin instillation and highest in the 14 days after bleomycin instillation. 4. In zymography, the active forms of MMP-2 were significantly increased as a result of the $IFN-{\gamma}$ treatment 3 days after the bleomycin instillation, bleomycin+$IFN-{\gamma}$ group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$209.63{\pm}7.60%:407.66{\pm}85.34%$, P<0.05), but 14 days after the bleomycin instillation, the active forms of MMP-2 were significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$159.36{\pm}20.93%:97.23{\pm}12.50%$, P<0.05). 5. The IL-4 levels were lower in the bleomycin and bleomycin+$IFN-{\gamma}$ groups but this was not significant, and the IL-13 levels showed no difference between the experiment groups. Conclusion : The author found that lung inflammation was increased in the early period but the pulmonary fibrosis was inhibited in the late stage as a result of $IFN-{\gamma}$. The inhibition of pulmonary fibrosis by $IFN-{\gamma}$ appeared to be associated with the inhibition of MMP-2 activation by $IFN-{\gamma}$. Further studies on the mechanism of the regulation of MMP-2 activation and the effects of MMP-2 activation on pulmonary fibrosis is warranted in the future.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.1
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• pp.39-44
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• 2006

Type I diabetes (T1D) is an organ-specific autoimmune disease caused by the T cell-mediated destruction of the insulin-producing ${\beta}$ cells in the pancreatic islets. The onset of T1D is the consequence of a progressive destruction of islet ${\beta}$ cells mediated by an imbalance between effector $CD4^+$ T helper (Th)1 and regulatory $CD4^+$ Th2 cell function. Since interferon-alpha (IFN-${\alpha}$) has been known to modulate immune function and autoimmunity, we investigated whether administration of adenoviralmediated IFN-${\alpha}$ gene would inhibit the diabetic process in NOD mice. The development of diabetes was significantly inhibited by a single injection of adenoviral-mediated IFN-${\alpha}$ gene before 8 weeks of age. Next, we examined the hypothesis that Th2-type cytokines are associated with host protection against autoimmune diabetes, whereas Th1-type cytokines are associated with pathogenesis of T1D. The expression of IFN-${\alpha}$ induced increase of serum IL-4 and IL-6 (Th2 cytokines) levels and decrease of serum IL-12 and IFN-${\gamma}$ (Th1 cytokines) levels. Therefore, overexpression of IFN-${\alpha}$ by adenoviralmediated delivery provides modulation of pathogenic progression and protection of NOD mice from T1D.

• Journal of Microbiology and Biotechnology
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• v.15 no.2
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• pp.265-268
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• 2005

To study the effect of bifidobacteria on preventing allergy response, levels of IFN-$\gamma$, IgG2a, IL-4, and IgG1 were investigated in splenocytes isolated from ovalbumin (OVA)­sensitized allergic mice and BGN4-administered allergy­suppressed mice in the presence of various bifidobacterial strains. Most of the bifidobacteria, except 2A, increased production of Th I-associated immune markers, IFN -$\gamma$ and IgG2a. In addition, most of the bifidobacteria, except 2A and 19A, decreased production of IL-4, whereas the differences in the production of IgG1 were less pronounced. These results suggest that some strains of bifidobacteria may have the potential to prevent the occurrence of allergy by switching Th1/Th2-type antibodies and/or related cytokines.

• IMMUNE NETWORK
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• v.3 no.1
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• pp.61-68
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• 2003

Background: Fibroblast functions both as a structural element and as a vital immunoregulatory cell. Fibroblasts regulate inflammation through governing of chemokine expression. In order to elucidate the mechanisms by which the expressions of chemokines were regulated, the co-stimulatory effects of Th1 and proinflammatory cytokines were compared using nasal mucosal fibroblasts. Methods: Human nasal mucosa was obtained from surgery for septal deviation and the growth of fibroblasts was established. Fibroblasts from 4th to 6th passage were stimulated with various combinations of cytokines. To inhibit selected signaling pathways, fibroblasts were pretreated with cyclosporin A, wortmannin, staurosporine, and dexamethasone prior to the stimulation with cytokines. The supernatants were collected and chemokines were detected with a sandwich enzyme-linked immunosorbent assay. Results: $TNF-{\alpha}/IFN-{\gamma}$-induced production of RANTES was inhibited by all inhibitors used. MCP-1 was produced constitutively and $TNF-{\alpha}$-induced or $TNF-{\alpha}/IFN-{\gamma}$-induced production of MCP-1 was not inhibited by cyclosporin A or wortmannin, but by stauroporine or dexamethasone. All inhibitors used in this experiment inhibited $TNF-{\alpha}/IFN-{\gamma}$-induced or $IL-1{\beta}/IFN-{\gamma}$-induced production of MCP-2 in nasal mucosal fibroblasts. Although staurosporine or dexamethasone showed strong inhibitory effects, cyclosporin A or wortmannin did not inhibit the production of MCP-3 by $IL-1{\beta}/IFN-{\gamma}$ treatment. Conclusion: Chemokines were strongly induced by stimulation of cytokines in combination and showed different pattern of inhibition by the inhibitors. Therefore, it was assumed that cytokines acted on multiple pathways or on unknown pathways which converged to gene-specific transcription factors.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.922-927
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• 2005

In the present study, baicalin, baicalein, and wogonin, a major flavone isolated from Scutellaria Radix were examined for their effects on PMA-induced Interlukin-6 (IL-6), $interferon-\gamma(IFN-\gamma)$, tumor necrosis factor $(TNF)-\alpha$, IL-4, IL-10, and IL-13 productions in the PMA-stimulated $CD4^+$ Jurkat T cells. These three compounds inhibited PMA-induced Th1 cytokine $(IL-6,\;IFN-\gamma,\;TNF-\alpha)$ and Th2 cytokine (IL-4 and IL-13) productions in a concentration-dependent manner. But wogonin, but not baicalin baicalein, increased PMA-induced IL-10 production. These results suggest that baicalin, baicalein, and wogonin, a major flavone modulate Th1 and Th2 cytokine productions in $CD4^+$ Jurkat T cells and these properties may contribute to the anti-atopic dermatitis activity of Scutellaria Radix.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.4
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• pp.754-761
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• 2008

The purpose of this study was to evaluate the effect of Baekhasuoyijung-Tang(BHSYJT)on mouse T cell cytokines. The proliferation of mouse CD4 T cells under the influence of BHSYJT extract was measured. When mouse CD4 T cell were stimulated with anti-CD3 and anti-CD28 in various concentrations of BHSYJT extract, it increased proliferation of CD4 cells by 28% in $10{\mu}g/m{\ell}$ concentration and by 32% in $100{\mu}g/m{\ell}$ concentration. Treatment of CD4+ T cells stimulated by anti-CD3e and anti-CD28 with BHSYJT resulted in reduction of $IFN-{\gamma}$,but IL-4 levels is not changed. Oral administration of BHSYJT resulted in increase of both CD4+ and CD8+ T cell population in Balb/c mice by 11%. Oral administration of BHSYJT resulted in reduction of serum $IFN-{\gamma}$ level by 27% but, IL-4 level is not changed. CD4+ T cells under Th1/Th2 polarizing conditions for 3 days with BHSYJT resulted in decrease of $IFN-{\gamma}$ level in TH1 cells. Experimental results of this study show that BHSYJT helps to reduce secretion of $IFN-{\gamma}$ by mouse T helper cell in vitro and it had the same effect in vivo. Thus, it can be concluded that use of BHSYJT is an effective treatment for correcting immune imbalance in immune disorders and autoimmune diseases by reducing secretion of cytokine by Th1 cells.

• Preventive Nutrition and Food Science
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• v.11 no.1
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• pp.54-60
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• 2006

The immunomodulatory effect of a new herbal preparation, HemoHIM, on the recovery from leukopenia induced by cyclophosphamide treatment was investigated. The HemoHIM was made up with an addition of the ethanol-insoluble fraction to the total water extract of Angelica Radix, Cnidii Rhizoma and Paeonia Radix. Daily oral administration of 100 mg/kg BW or 500 mg/kg BW HemoHIM accelerated the recovery from cyclophosphamide-induced leukopenia. HemoHIM increased the number of leukocytes and lymphocytes in the peripheral blood when compared with the cyclophosphamide-treated control. Moreover, the suppressed natural killer (NK) cell activity and interferon $(IFN)-{\gamma}$ secretion in the cyclophosphamide-treated mice were restored by the administration of HemoHIM. HemoHIM significantly reduced the abnormally heightened ratio of interleukin $(IL)-4/IFN-{\gamma}$ and immunoglobulin (Ig)E/IgG2a in the cyclophosphamide-treated mice. These results suggest that HemoHIM accelerates the recovery from leukopenia and alleviates the imbalanced T helper (Th)l/Th2 responses in the cyclophosphamide-treated mice. Additionally, HemoHIM was found to stimulate normal splenocytes to secrete not only Thl type cytokines such as $IFN-{\gamma}$ and IL-2, but also Th2 type cytokine IL-4. In conclusion, our results show that HemoHIM certainly has an influence on the balanced recovery of immune cells and the activation of their activities in the cyclophosphamide-treated mice.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.22 no.1
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• pp.120-132
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• 2009

Objective : Yukmijihwang-tang is one of the important medicines for blood- deficiency and yin-deficiency. Atopic dermatitis usually shows dampness-heat pattern in its acute stage and blood-deficiency or yin-deficiency pattern in its chronic stage. Therefore, I hypothesized that Yukmijihwang-tang is effective on atopic dermatitis and investigated the effects of Yukmijihwang-tang on NC/Nga mice's atopic dermatitis induced by DNCB. Methods : The NC/Nga mice with atopic dermatitis were divided into four groups: three experimental groups and one control group. The experimental groups were respectively put on 2.5g(YM-2.5), 5g(YM-5) and 10g(YM-10) of Yukmijihwang-tang extract per their weight once a day for 10 days while the control group was fed normal saline. After 10 days, I measured TEWL(transepidermal water loss), observed scratching behaviors, conducted a skin biopsy and checked levels of Total IgE, IL-4 and $IFN-\gamma$ on NC/Nga mice. Results : 1. Yukmijihwang-tang significantly suppressed skin dryness. In particular, YM-5 and YM-10 had better skin hydration than YM-2.5. 2. Yukmijihwang-tang significantly suppressed pruritus while there was no significant difference among the experimental groups. 3. Yukmijihwang-tang retained skin structure(epidermis, dermis and subcutaneous fat). 4. Yukmijihwang-tang reduced Total IgE level while there was no significant difference between the control group and the experimental groups. 5. Yukmijihwang-tang did not reduce IL-4(Th2 cytokine) level. 6. Yukmijihwang-tang significantly reduced $IFN-\gamma$(Th1 cytokine) level. In particular, YM-2.5 and YM-5 had lower $IFN-\gamma$ level than YM-10. Conclusion : The results suggest that Yukmijihwang-tang suppresses skin dryness and pruritus, retains skin structure and is effective on chronic atopic dermatitis which is associated with Th1 cytokines in the immune response.