• Tuberculosis and Respiratory Diseases
• /
• v.45 no.2
• /
• pp.301-310
• /
• 1998

Background: Cell mediated immune response mediated by interaction between CD4+ T lymphocytes and macrophagies is thought to play an important role in tuberculous pleurisy. This interaction is dependent on the interplay of various cytokines. The immunologic response of tuberculous pleurisy is thought to depend on the balance between helper T cell(Th1) cytokine Interleukin-12, Interferon gamma and Th2 cytokine IL-4, IL-10. To understand immunologic mechanism in tuberculous pleurisy and evaluate diagnostic value of these cytokines, the concentrations of Th1 cytokine IL-12, IFN -$\gamma$ and Th2 cytokine IL-10 were measured in tuberculous pleurisy and malignant pleural effusion group. Material and Methods: The concentrations of IL-10, IL-12 and IFN-$\gamma$ were measured by ELISA method in pleural fluids and serums of 20 patients with tuberculous pleurisy and 20 patients with malignant pleural effusion ADA activities were measured by spetrophotomery in pleural fluids of both groups. Results: In tuberculous pleurisy, the mean concentrations of IL-10, IL-12 and IFN-$\gamma$ of pleural fluids showed $121.3{\pm}83.7$ pg/mL, $571.4{\pm}472.7$ pg/mL and $420.4{\pm}285.9$ pg/mL. These were significantly higher than that of serum, $21.2{\pm}60.9$ pg/mL, 194.5 pg/mL, $30.1{\pm}18.3$ pg/mL respectively(p< 0.01). In malignant pleural effusion, the mean concentrations of IL-10, IL-12 and IFN-$\gamma$ of pleural fluids showed $88.4{\pm}40.4$ pg/mL, $306.5{\pm}271.1$ pg/mL and $30.5{\pm}54.8$ pg/mL respectively. Compared with that of serum ($43.4{\pm}67.2$ pg/mL, $206.8{\pm}160.6$ pg/mL, $14.6{\pm}3.3$ pg/mL), only IL-10 was significantly higher (p<0.001), but IL-12, IFN-$\gamma$ were not significant. In tuberculous pleural effusion compared with malignant pleural effusion, the concentration of IL-12, IFN-$\gamma$, ADA were significantly higher (p=value 0.046, <0.001, <0.001), but IL-10 was not significant. For differential diagnosis of tuberculous pleurisy from malignant pleural effusion, using cut-off value of IL-12, IFN-$\gamma$, ADA as 300 pg/mL. 100 pg/mL, 45 U/L, the sensitivity/specificity were 60%/70%, 90%/87.5%, 85%/90% respectively. Conclusion: In tuberculous pleurisy, IL-10, IL-12 and IFN-$\gamma$ were selectively concentrated highly in pleural space than serum. Compared with malignant pleural effusion, IL-12 and IFN-$\gamma$ were significantly higher, but IL-10 were not in tuberculous pleural effusion. The results suggest that Th1 pathway contributes to immune resistant mechanism in tuberculous pleurisy. IFN-$\gamma$ and ADA revealed useful methods of differential diagnosis in tuberculous pleurisy from malignant pleural effusion.

• The Journal of Pediatrics of Korean Medicine
• /
• v.30 no.4
• /
• pp.29-59
• /
• 2016

Objectives PRAL (Prunus armeniaca Linne Var) has been known to suppress allergic reaction. However, the cellular target and its mechanism of action were unclear. This study was designed to investigate the effect of PRAL on RBL-2H3 mast cell, which is PMA-Ionomycin-induced activated in vitro and the effect of PRAL on the MNC/Nga mice that are DNCB-induced activated in vivo. Methods In this study, IL-4, IL-13 production were examined by ELISA analysis; IL-4, IL-13, IL-31, IL-31Ra, $TNF-{\alpha}$ and GM-CSF mRNA expression were examined by Real-time PCR; manifestations of AP-1 and MAPKs transcription factors were examined by western blotting in vitro. Then skin rashes have been evaluated and verified the distribution of mast cells by H&E and toluidine blue. Also, WBC, eosinophil and neutrophil, IgE level in serum, $IFN-{\gamma}$, IL-4, IL-5 in the splenocyte culture supernatant, the absolute cell numbers of $CD4^+$, $CD8^+$, $Gr-1^+CD11b^+$, $B220^+CD23^+$, $CD3^+CD69^+$ in the Axillary Lymph Node (ALN), PBMCs and dorsal skin and IL-5, IL-13, IL-31, IL-31Ra in the dorsal skin by Real-time PCR were all evaluated from the NC/BNga mice. Results As a result of this study, the mRNA expression of IL-4, IL-13, IL-31, IL-31Ra and $TNF-{\alpha}$ and IL-4, IL-13 production, shown in ELISA analysis, were suppressed by PRAL. Results from the western blot analysis showed decrease on the expression of mast-cell-specific transcription factors, including AP-1 and p-JNK, p-ERK. Histological examination showed that infiltration levels of immune cells in the skin of the AD-induced NC/Nga mice were improved by PRAL orally adminstration. Orally- administered PRAL group also showred decreased level of IgE in the serum. This group has shown decreased the level of IL-4, IL-5, but shown elevated $IFN-{\gamma}$ level in the splenocyte culture supernatant. The same group also has shown decreased cell numbers of $CD4^+$, $CD8^+$, $CD3^+CD69^+$ in the ALN, and $CD4^+$, $Gr-1^+CD11b^+$ in the dorsal skin. PRAL oral adminstration increased cell numbers of $CD4^+$, but decreased cell numbers of $CD8^+$, $Gr-1^+CD11b^+$, $B220^+CD23^+$ in the PBMCs. Conclusions Obtained results suggest that PRAL can regulate molecular mediators and immune cells that are functionally associated with atopic dermatitis (AD) induced in the NC/Nga mice. This may play an important role in recovering AD symptoms and suppressing pruritus.

• Korean Journal of Pharmacognosy
• /
• v.43 no.3
• /
• pp.224-230
• /
• 2012

Schizandrin (SZ), was isolated from the fruit of Schizandra chinensis, has been reported to have many biological properties, including anti-inflammatory and antitumor activities. However, its anti-allergic effects are not completely elucidated. We focused on the anti-allergic effects of SZ in PMA/ionomycin (PI)-induced rat basophilic leukemia (RBL-2H3) cells and P815 mast cells. Cytokines (IL-4, IL-13), synthesized by basophils and mast cells, are implicated in pathological conditions such as asthma and allergy. The production of IL-4 and IL-13 was quantified by ELISA and the mRNA expression was detected by using RT-PCR assay. In this study, we found that SZ did not show cytotoxic effect at up to 100 ${\mu}M$ on RBL-2H3 cells and mast cells. In addition, SZ inhibited the production of IL-4 and IL-13 and also decreased the level of mRNA in PI-induced RBL-2H3 cells and mast cells in a dose-dependent manner. Thus, we suggest that SZ may have the effect on preventing allergic disorders by inhibiting IL-4 and IL-13 cytokines.

• The Journal of Pediatrics of Korean Medicine
• /
• v.26 no.1
• /
• pp.1-15
• /
• 2012

$CheongGiGeoYangTang$ has been used for anti-allergenic purpose. However there was no experimental study about its effect. Therefore, this study was designed to investigate the anti-allergenic effect of $CheongGiGeoYangTang$. Methods Modifiability of RBL-2H3 mast cells' IL-4, IL-13 was analyzed by qRT-PCR and ELISA. Also, the suppressive effect of GATA-1, GATA-2, NF-AT1, NF-AT2, AP-1 and NF-${\kappa}B$ p65 transcription factors was observed by western blotting. OVA-specific IgE, IL-4 and IL-13 production in ovalbumin allergy model was examined as well. Results It was showed that the RBL-2H3 mast cells treated with $CheongGiGeoYangTang$ extract(CGGYT) was significantly suppressed mRNA expression, production of IL-4 and IL-13, and prominently inhibited the expression of transcription factors including GATA-1, GATA-2, NFAT-1, NFAT-2, c-Fos and NF-${\kappa}B$ p65 but not c-Jun. The administration of CGGYT was suppressed the amount of OVA-specific IgE, IL-4 and IL-13 in OVA/alum-sensitized mice. Conclusions We considered CGGYT would regulate the allergic inflammation as inhibition of IL-4 and IL-13 production in activated mast cells and Th2 cells.

• Advances in Traditional Medicine
• /
• v.2 no.2
• /
• pp.113-118
• /
• 2002

Falun Gong (FG) is an advanced system of cultivation and practice, which is beneficial for both mind and body. In this study we investigated the effects of FG on the production of cytokines in FG practitioner (FGP). To study whether plasma cytokines levels were affected by FG, their levels were analyzed. The amount of $interferon-{\gamma}$ $(IFN-{\gamma})$, interleukin (IL)-2, IL-4 and IL-6 (2.5-fold for $IFN-{\gamma}$, 1.2-fold for IL-2, 2.1-fold for IL-4 and 2.5-fold for IL-6, respectively) were significantly higher in the FGP group than normal group (P<0.05). Peripheral blood mononuclear cells obtained from normal healthy control and FGP were cultured for 24 h in the presence or absence of lipopolysaccharide. The amount of $IFN-{\gamma}$, IL-2, IL-4 and IL-6 in culture supernatant was quantified. However, there were no significant differences in the level of the same cytokines between the normal and FGP group. These data suggest that FG cultivation may contribute to immune-enhancement in vivo.

• Childhood Kidney Diseases
• /
• v.9 no.2
• /
• pp.175-182
• /
• 2005

Purpose : Interleukin 1 receptor antagonist(IL-1ra) is an endogenous antiinflammatory agent that binds to IL-1 receptor and thus competitively inhibits the binding of IL-1$\alpha$ and IL-1$\beta$. Allele 2 in association with various autoimmune diseases has been reported. In order to evaluate the influence of IL-1ra gene VNTR polymorphism on the susceptibility to HSP and its possible association with disease severity, manifested by severe renal involvement and renal sequelae, we studied the incidence of carriage rate and allele frequency of the 2 repeats of IL-1ra allele 2($IL1RN^{*}2$) of the IL-1ra gene in children with HSP with and without renal involvement. Methods : The IL-1ra gene polymorphisms were determined in children with HSP with(n=40) or without nephritis(n=34) who had been diagnosed at Busan Paik Hospital and the control groups(n=163). Gene polymorphism was identified by PCR amplification of the genomic DNA. Results : The allelic frequency and carriage rate of $IL1RN^{*}1$ were found most frequently in patients with HSP and in controls. The allelic frequency of $IL1RN^{*}2$ was higher in patients with HSP compared to that of controls($4.7\%\;vs.\;2.5\%$, P=0.794). The carriage rate of $IL1RN^{*}2$ was higher In patients with HSP compared to that of controls($8.1\%\;vs.\;6.8\%$, P=0.916). The allelic frequency of $IL1RN^{*}2$ was higher in patients with HSP nephritis compared to that of HSP($5.3\%\;vs.\;2.9\%$, P=0.356). The carriage rate of $IL1RN^{*}2$ was higher in Patients with HSP nephritis compared to that of HSP($10.0\%\;vs.\;5.9\%$, P=0.523). Among 13 patients with heavy proteinuria(>1.0 g), 11 had $IL1RN^{*}1$, 1 had $IL1RN^{*}2$ and the others had $IL1RN^{*}4$. At the time of last follow up 4 patients had sustained proteinuria and their genotype was $IL1RN^{*}1$. Conclusion : The allelic frequency and carriage rate of $IL1RN^{*}1$ were found most frequently in patients with HSP and in controls. Our study suggests that the carriage rate and allele frequency of the 2-repeats of IL-1lra allele 2($IL1RN^{*}2$) of the IL-1ra gene may not be associated with susceptibility and severity of renal involvement in children with HSP (J Korean Soc Pediatr Nephrol 2005;9:175-182)

• Genomics & Informatics
• /
• v.3 no.4
• /
• pp.149-153
• /
• 2005

Asthma is an inflammatory airways disease characterized by bronchial hyperresponsiveness and airways obstruction, which results from a complex interaction of genetic and environmental factors. Interleukin (IL)-13 and IL-4 are important in IgE synthesis and allergic inflammation, therefore genes encoding IL-13 and IL-4 are candidates for predisposition to asthma. In the present study, we screened single-nucleotide polymorphisms (SNPs) in IL-13 and IL-4 and examined whether they are risk factors for asthma. We resequenced all exons and the promoter region in 12 asthma patients and 12 normal controls, and identified 18 SNPs including 2 novel SNPs. The linkage disequilibrium(LD) pattern was evaluated with 16 common SNPs, and haplotypes were also estimated within the block. Although IL-13 and IL-4 are localized within 27 kb on chromosome 5q31 and share many biological profiles, this region was partitioned into 2 blocks. One SNP and three SNPs were determined as haplotype-taggingSNPs (htSNPs) within IL-13 and IL-4 haplotype-block, respectively. No significant associations were observed between any of the SNPs or haplotypes and development of asthma in small number of Korean subjects. However, the genetic variants of IL-13 and IL-4 would provide valuable strategies for the genotyping studies in large population.

• Archives of Pharmacal Research
• /
• v.17 no.3
• /
• pp.194-198
• /
• 1994

The antitumor effects of the 2E4 and anti--Tac, monoclonal antibodies directed to Il-2 receptor (IL-2R) conjugated with .alpha.-particle emitting radionuclide bismuth-212., were compared. The $^{212}Bi-2E4$ demonstratedspecific cytotocicity to EL4J3, 4, a I$L-2R^+$ cell line, than to EL4J, a $IL-2R^-$ cell line in thymidine incorporation assy. TEX>$^{212}Bi-2E4$ exerted the maximal antitumor effect in that % T/C in C57BL/6 mice implanted with EL4J3.4 ascitic tumor was 331% at the concentration of $50{\;}{\mu}Ci$, while that of $^{212}Bi-anti-Tac$ was 258% at $100{\;}{\mu}Ci$.

• The Journal of Internal Korean Medicine
• /
• v.21 no.1
• /
• pp.31-38
• /
• 2000

Background : Nowadays asthma is considered to be the inflammatory disease characterized by airway hyperresponsiveness and pulmonary eosinophilia, and mediated by Th lymphocytes expressing the Th2 cytokine pattern. In many recent studies, molecular biological methods have been used to investigate the role of cytokines in pathogenesis and new therapeutic targets of asthma. Objective : We aimed to identify the effect of Armeniacae Arnarum Semen and Platycodi Radix on the transcriptional activities of cytokine IL-4, IL-5 and IL-6 involved in asthma model. Materials and Methods : RBL-2H3 cell lines were used. Cells were stimulated with calcium inophore for maximal gene expression. After 24 hours of Armeniacae Arnarum Semen and Platycodi Radix-treatment, total cellular RNAs were collected using Trizol solution method. Then transcriptional activities of IL-4, IL-S and IL-6 were measured by RT-PCR with electrophoresis. Results : In IL-4 study, Armeniacae Arnarum Semen treated group showed 48.4% of transcriptional activities compared to the control group and Platycodi Radix treated group showed 45.4% of transcriptional activities compared to the control group. In IL-5 study, Armeniacae Arnarum Semen treated group showed 52.7%of transcriptional activities compared to the control group and Platycodi Radix treated group showed 60.2% of transcriptional activities compared to the control group. In IL-6 study, Armeniacae Amarum Semen treated group showed 42.3% of transcriptional activities compared to the control group and Platycodi Radix treated group showed 69.1% of transcriptional activities compared to the control group. Conclusion : This study shows that Armeniacae Arnarum Semen and Platycodi Radix have the inhibitory effect on the transcription of IL-4, IL-5 and IL-6 gene expression in RBL-2H3 cell lines. Advanced studies are required to investigate the mechanisms of inhibition by herbal medicine in asthma model.

• Tuberculosis and Respiratory Diseases
• /
• v.43 no.3
• /
• pp.348-358
• /
• 1996

Background : Interleukin-5 (IL-5) is responsible for eosinophilia in allergic diseases. In allergic bronchial asthma, there is a correlation between the extent of eosinophil infiltration in bronchial mucosa and IL-5 concentrations. In addition, IL-2 concentration is elevated in the airways and associated with eosinophilia in symptomatic patients with bronchial asthma. In animal studies, IL-2 can induce eosinophilia by increasing the synthesis of IL-5, however, it is still unknown how IL-2 can induce eosinophila in human being. The aim of this study is to evaluation the effect and mechanism of IL-2 on prolongation of eosinophil survival. Methods : After purifiing the eosinophils from the venous blood of allergic patients with eosinophilia, we measured the survival rates of eosinophils using trypan blue dye exclusion test, and the number of eosinophils with Randolp's solution. We compared the survival rates of eosinophils in the presence of IL-2 or IL-5. Neutralizing antibody for IL-5 was added in IL-2 treated eosinophils to reveal whether IL-2 induced prolongation of eosinophil survival was mediated by IL-5. We checked IL-5 m-RNA expression of lymphocytes in the presence of IL-2 by using Reverse transcription-Polymerase chain reaction (RT-PCR) method to revealed the effect of IL-2 on IL-5 m-RNA expression on lymphocyte. $\alpha$ and $\beta$ IL-2 receptors were measured on eosinophils and lymphocytes with flow-cytometer after stimulated with IL-2. Results : 1) Eosinophil survival rates increased dose dependently on IL-5 and IL-2. 2) The eosinophil survival rates increased by IL-2 were not inhibited by the pretreatment with neutralizing antibody for IL-5. 3) IL-5 m-RNA was not expressed on lymphocytes by the treatment with IL-2 up to 96 hours. 4) IL-2 upregulate the expression of IL-$2R{\alpha}$ on eosinophils, instead of no effect on the expression of IL-$2R{\beta}$. Conclusion: Interleukin-2 had the enhancing effect on the survival rates of eosinophils. The mechanism behind IL-2 induced eosinophilia might be the increment of IL-2 receptors on eosinophils rather than IL-5 synthesis by lymphocytes.