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

• Journal of Chest Surgery
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• v.38 no.12 s.257
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• pp.807-814
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• 2005

Background: Cardiopulmonary bypass is an essential process to maintain circulation for saving life during the cardiac surgery, But it is a process in which systemic inflammation was evoked inevitably because of the exposure of blood to foreign surface. The injuries to distal organs during the cardiopulmonary bypass were resulted from systemic inflammation and the disturbances of micro-circulations in the organs. We designed this study to research the effects of leukocyte depletion from pump-oxygenator priming solution on the systemic inflammation, and the micro-circulation of gastric mucosa that is suggested by the gastric mucosal $CO_{2}$ partial pressure and acidity. Material and Method: The dogs were divided into three groups according to the different pump-oxygenator priming solutions; non-hemic crystalloid solution; leukocyte-depleted homologous blood; and non leukocyte-depleted homo-logous blood. Each priming solution group contained five dogs. In all three groups, 2 hours of cardiopulmonary bypass, and 4 consecutive hours of general anesthesia was maintained on the mechanical ventilation. Each dog was evaluated for the gastric mucosal pH, $CO_{2}$ partial Pressure, arterial pH, $CO_{2}$ partial pressure, the exhaled air $CO_{2}$ partial pressure and the level of IL-8 on before the cardiopulmonary bypass, 1 hour after the cardiopulmonary bypass, 2 hours after the cardiopulmonary bypass, 2 hours after the restoration of normal circulation, and 4 hours after the restoration of normal circulation after the cardiopulmonary bypass. The levels of IL-8 were measured with ELISA (enzyme linked immunosorbent assay) technique. Result: 1. There were significant differences of gastric mucosal $CO_{2}$ partial pressure between the leukocyte-depleted homologous blood group and other two groups(vs non leukocyte-depleted homologous blood group; P=0.02, vs non-hemic crystalloid solution group; P=0,01). 2. The gastric mucosal pH of leukocyte-depleted homologous blood group was significantly different from non leukocyte-depleted homologous blood group (p=0.01). 3. The levels of IL-8, which examine the systemic inflammation, showed signi- ficantly better results in leukocyte-depleted homologous blood group and non-hemic crystalloid solution group than non leukocyte-depleted homologous blood group (p=0.01, 0.01). Conclusion: Based upon these results, we concluded that the leukocyte depletion from the pump-oxygenator priming solution has a beneficial effects in reducing systemic inflammation and the preserving of gastric mucosal micro-circulation.

• Korean Journal of Poultry Science
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• v.45 no.3
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• pp.201-207
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• 2018

An experiment was conducted to investigate the effect of fermented garlic solution (FGS) on the performance, egg quality and blood profiles of laying hens in the finishing period. In total, 432 Lohmann Brown hens aged 79 weeks were equally distributed into four dietary treatments with six replicate. Hens were fed the basal diet containing 2,750 kcal/kg of ME and 16% of CP, which was supplemented with either 0% (control), 0.05%, 0.10% and 0.20% FGS from 79 to 83 weeks old. Laying performance, egg quality, yolk fatty acids and serum characteristics were analyzed at the end of experiment. Egg production and feed conversion was numerically improved in FGS supplementation treatments compared to those in the control, but were not statistically different. The albumen height and Haugh unit showed significant increase (P<0.05) in the FGS supplementation groups. The concentration of saturated fatty acid decreased in the yolks of birds fed FGS (P<0.01), whereas the unsaturated fatty acid (UFA) and mono-UFA contents were significantly higher (P<0.01) in those treatments than in the control. Significantly lower natural fat and cholesterol in serum were observed in birds fed the 0.20% FGS supplementation diet (P<0.01). However, the high-density lipoprotein (HDL) cholesterol increased in both the 0.10% and 0.20% FGS supplementation groups. In addition, interleukin-2 mRNA and CD4+/CD8+ level in serum which were cellular immunity indicators showed statistical differences (P<0.01) among treatments and a higher concentration in the 0.10% and 0.20% FGS groups than in the control. Thus, it can be concluded that dietary supplementation of FGS improved egg quality and stimulated immune response in mature laying hens.

• Clinical and Experimental Pediatrics
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• v.53 no.4
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• pp.481-487
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• 2010

Purpose: Recently many studies show early exposure during childhood growth to endotoxin (lipopolysaccharides, LPS) and/or early exposure to allergens exhibit important role in development of allergy including bronchial asthma. The aim of this study was to evaluate the role of endotoxin and allergen exposure in early life via the airways in the pathogenesis of allergic airways inflammation and airway hyperresposiveness (AHR) in mouse model of asthma. Methods: Less than one week-old Balb/c mice was used. Groups of mice were received either a single intranasal instillation of sterile physiologic saline, 1% ovalbumin (OVA), LPS or $1.0{\mu}g$ LPS in 1% OVA. On 35th day, these animals were sensitized with 1% OVA for 10 consecutive days via the airways. Animals were challenged with ovalbumin for 3 days on 55th days, and airway inflammation, hyperresponsiveness, and cytokine expression were assessed. Measurements of airway function were obtained in unrestrained animals, using whole-body plethysmography. Airway responsiveness was expressed in terms of % enhanced pause (Penh) increase from baseline to aerosolized methacholine. Lung eosinophilia, serum OVA-IgE and bronchoalveolar lavage (BAL) fluid cytokine levels were also assessed. ANOVA was used to determine the levels of difference between all groups. Comparisons for all pairs were performed by Tukey-Kramer honest significant difference test; $P$ values for significance were set to 0.05. Results: Sensitized and challenged mice with OVA showed significant airway eosinophilia and heightened responsiveness to methacholine. Early life exposure of OVA and/or LPS via the airway prevented both development of AHR as well as bronchoalveolar lavage fluid eosinophilia. Exposure with OVA or LPS also resulted in suppression of interleukin (IL)-4, 5 production in BAL fluid and OVA specific IgE in blood. Conclusion: These results indicate that antigen and/or LPS exposure in the early life results in inhibition of allergic responses to OVA in this mouse model of astham. Our data show that early life exposure with OVA and/or LPS may have a protective role in the development of allergic airway inflammation and development of allergen-induced airway responses in mouse model of asthma.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.529-541
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• 2003

Yukmijihwang-tang has been widely used as an and-aging herbal medicine for hundred years in Asian countries. Numerous studies show that Yukmijihwangtang has anti-oxidative effect both in vivo and in vitro. It has been reported that Moutan Cortex Radicis extract (MCR) was the most effective herb in Yukmijihwang-tang on undifferentiated PC12 cells upon oxidative-stressed with hydrogen peroxide. The purpose of this study is to; 1) evaluate the recovery of neuronal damage by assessing the anti-oxidant effect of MCR on PC12 cells differentiated with nerve growth factor (NGF), 2) identify candidate genes responsible for anti-oxidative effect on differentiated PC12 cells by oligonucleotide chip microarray. PC12 cells, which were differentiated by treating with NGF, were treated without or with hydrogen peroxide in the presence or absence of various concentration of MCR. Cell survival was determined by using MTS assay. Measurement of intracellular reactive oxygen species (ROS) generation was determined using the H2DCFDA assay The viability of cells treated with MCR was significantly recovered from stressed PC12 cell. In addition, wide rage of concentrations of MCR shows dose-dependent inhibitory effect on ROS production in oxidative-stressed cells. Total RNAs of cells without treatment(Control group), only treated with H₂O₂ (stressed group) and treated with both H₂O₂ and of MCR (MCR group) were isolated, and cDNAs was synthesized using oligoT7(dT) primer. The fragmented cRNAs, synthesized from cDNAs, were applied to Affymetrix GeneChip Rat Neurobiology U34 Array. mRNA of Calcium/calmodulin-dependent protein kinase II delta subunit(CaMKII), neuron glucose transporter (GLUT3) and myelin/oligodendrocyte glycoprotein(MOG) were downregulated in Stressed group comparing to Control group. P2X2-5 receptor (P2X2R-5), P2X2-4 receptor (P2X2R-4), c-fos, 25 kDa synaptosomal attachment protein(SNAP-25a) and GLUT3 were downregulated, whereas A2 adenosine receptor (A2AR), cathechol-O-methyltransferase(COMT), glucose transporter 1 (GLUT1), EST223333, heme oxygenase (HO), VGF, UI-R-CO-ja-a-07-0-Ul.s1 and macrophage migration inhibitory factor (MIF) were upregulated in MCA group comparing to Control group. Expression of Putative potassium channel subunit protein (ACK4), P2X2A-5, P2X2A-4, Interferon-gamma inducing factor isoform alpha precursor (IL-18α), EST199031, P2XR, P2X2 purinoceptor isoform e (P2X2R-e), Precursor interleukin 18 (IL-18) were downregulated, whereas MOO, EST223333, GLUT-1, MIF, Neuronatin alpha, UI-R-C0-ja-a-07-0-Ul.s1, A2. adenosine receptor, COMT, neuron-specific enolase (NSE), HO, VGF, A rat novel protein which is expressed with nerve injury (E12625) were upregulated in MCR group comparing to Stressed group. The results suggest that decreased viability and AOS production of PC12 cell by H₂O₂ may be, at lease, mediated by impaired glucose transporter expression. It is implicated that the MCR treatment protect PC12 cell from oxidative stress via following mechanisms; improving glucose transport into the cell, enhancing expression of anti-oxidative genes and protecting from dopamine cytotoxicity by increment of COMT and MIF expression. The list of differentially expressed genes may implicate further insight on the action and mechanism behind the anti-oxidative effects of herbal extract Moutan Cortex Radicis.

• Journal of Animal Science and Technology
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• v.50 no.2
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• pp.185-198
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• 2008

Influences of dietary brown seaweed(BSW) on the nutrient metabolism, anti-oxidant enzyme activity and cell-mediated immune response were studied in broiler chicks activated acute phase response. 72 Hatched male broiler chicks(Ross) were divided into 12 pens, 6 heads per pen, and fed the BSW 0.0% (Basal) or 2.0% diet, respectively, and injected with the Salmonella typhimurium lipopoly saccharide(LPS) for activation of the acute phase response three times at 8, 10 and 12 d of age. During 4 wks of experimental feeding, growth performance of broiler chicks was not affected by dietary BSW and the acute phase response. Compared with control birds, the acute phase response did not affect the daily weight gain in birds fed BSW 2.0% diet, decreased nitrogen balance(NB) or metabolizable energy(ME) utilization per metabolic body size(kg0.75), and enhanced activities of peroxidase or extracellular SOD(EcSOD), tumor necrosis factor-alpha and ovotransferrin in plasma and MnSOD and CuZnSOD in erythrocyte cytosol. Compared to BSW 0.0% diet, 2.0% diet enhanced protein retention(NB) per kg0.75 regardless the acute phase response, did not affect uric acid nitrogen excretion(UAN) per kg0.75 in birds during the acute phase response, decreased(p<0.05) the UAN excretion per kg0.75 in control birds. And BSW 2.0% diet also decreased(p<0.05) plasma peroxide level and erythrocyte peroxidase or MnSOD activity but increased plasma peroxidase and EcSOD activity and interleukin-1 activity secreted from LPS-stimulated PBMC in 4 week broiler chicks.

• Tuberculosis and Respiratory Diseases
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• v.55 no.2
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• pp.140-153
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• 2003

Background : The cell-mediated immune reaction to tuberculosis infection involves a complex network of cytokines. The extent of inflammation, tissue damage and severity of the disease suggested to be determined by the balance between extent and duration of the proinflammatory cytokine response versus those of the suppressive cytokines. The systemic cytokine response in pathogenesis of tuberculosis can be assessed by measuring serum cytokine levels. Method : Serum interleukin-1 beta(IL-$1{\beta}$), IL-2, IL-4, IL-6, IL-10, IL-12(p40), tumor necrosis factor-alpha(TNF-${\alpha}$), interferon-gamma(IFN-${\gamma}$) and transforming growth factor-beta(TGF-${\beta}$) levels were measured in 83 patients with pulmonary tuberculosis, 10 patients with endobronchial tuberculosis before treatment and 20 healthy subjects by using a sandwich ELISA. In patients with pulmonary tuberculosis, they were divided into mild, moderate and far advanced group according to the severity by ATS guidelines. To compare with those of pretreatment levels, we measured serum IL-$1{\beta}$, IL-2, IL-4, IL-6, IL-10, IL-12(p40), TNF-${\alpha}$, IFN-${\gamma}$ and TGF-${\beta}$ levels in 45 of 83 patients with pulmonary tuberculosis after 2 and 6 months of treatment. Results : 1) In sera of patients with active pulmonary tuberculosis(n=83), IL-$1{\beta}$, IL-6(p<0.05), TNF-${\alpha}$, and IFN-${\gamma}$ were elevated and TGF-${\beta}$ was decreased comparing to control. IL-2, Il-12(p40), IL-4 and IL-10 were similar between the patients with tuberculosis and control. 2) In endobronchial tuberculosis, IL-6 and TNF-${\alpha}$ were elevated and TGF-${\beta}$ was decreased comparing to control. IL-12(p40) seemed to be elevated comparing to pulmonary tuberculosis. 3) Far advanced tuberculosis showed markedly elevated IL-6 and IFN-${\gamma}$ level(p<0.05). 4) The significant correlations were noted between IL-1, IL-6 AND TNF-${\alpha}$ and between IL-12, Il-2 and IL-4(p<0.01). 5) After 2 and 6 months of standard treatment, the level of IL-6 and IFN-${\gamma}$ was significantly decreased(p<0.05). Conclusion : These results showed that an altered balance between cytokines is likely to be involved in the extent of inflammation, tissue damage and severity of the disease tuberculosis. But, it should be considered diversities of cytokine response according to type of tuberculosis and immunity in clinical application and interpreting future studies.

• Journal of Periodontal and Implant Science
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• v.26 no.3
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• pp.641-654
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• 1996

In infectious disease, invasion of host tissue by bacteria or their products frequently induces a wide variety of inflammatory and immunopathologic reaction. Evidence indicates that cytokines are involved in the initiation and progression of chronic inflammatory diseases, such as periodontitis. Interleukin-6, which is a multifunctional cytokine, has important roles in acute and chronic inflammation and may also be implicated in bone resorption. Periodontal diseases are characterized by chronic inflammation of the periodontium with alveolar bone resoption. A principal driving force behind this response appears to lie in the immune system's response to bacteria. Many of the cell components which have been shown to function as virulence factors in gram-negative bacteria are associated with the bacterial surface. Of these, lipopolysaccharide has been characterized as one that mediates a number of biological activities which can lead to the destruction of host tissue. Non-steroidal antiinflammatory drug is used for reduce inflammation, and most of NSAIDs inhibit prostaglandine $E_2$ production, but it is shown that $PGE_2$ production is stimulated by IL-1 in recent study. So, the influence of other cytokines except $PGE_2$ on periodontium can not be avoided. Therefore, new antiinflammatory drug is needed. Rhizoma coptidis is used in oriental medicine for anti-inflammation and antiseptics. In this present study, we examined the IL-6 release in periodontal ligament cells treated with the lipopolysaccharide, and also the effect of rhizoma coptidis on cellular activity and IL-6 production of periodontal ligament cells. To evaluate the effect of rhizoma coptidis on cellular activity, the cells were seeded at a cell density of $1{\times}10^4$ cells/well in 24-well culture plates. After one day incubation, 1-6, 10-9 and 10-12 g/ml of rhizoma coptidis and 5, $10{\mu}g/ml$ of LPS were added to the each well and incubated for 1 and 2 days, respectively. Then, MTT assay were carried out. To evaluate the effect of rhizoma coptidis on IL-6 production, the cells were seeded at a cell density of $1.5{\times}10^4$ cells/well in 24-well culture plates. After one day incubation, 10-9 g/ml of rhizoma coptidis and 5, $10{\mu}g/ml$ of LPS were added to the each well and incubated for 3, 6, 12 and 24 hours. Then, amounts of IL-6 production is measured by IL-6 ELISA kit used. The results were as follows : 1. Rhizoma coptidisrbelow to ($10^{-6}g/ml$) significantly increaed cellular activity of periodontal ligament cells than control. 2. Rhizoma coptidist ($10^{-9}g/ml$) significantly increased cellular activity of LPS($5{\mu}g/ml$)-treated periodontal ligament cells than control. 3. LPS(5 and $10{\mu}g/ml$) significantly increased IL-6 production of periodontal ligament cells than control. 4. Rhizoma coptidis($10^{-9}g/ml$) decreased IL-6 production of LPS ($5{\mu}g/ml$)-treated periodontal.ligarnent cells than LPS only tested group. These findings suggest that stimulation of the IL-6 release of periodontal ligament cells by LPS may have a role in the progression of inflammation and alveolar bone resoption in periodontal disease, and that inhibition of the IL-6 release of cells and stimulation of cellular activity by rhizoma coptidis may help the periodontal regeneration.

• Journal of Life Science
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• v.28 no.1
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• pp.17-25
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• 2018

In this study, we examined the efficacy of the immune regulation of ${\beta}$-1,3/1,6-glucan and Lactobacillus plantarum LM1004 on atopic dermatitis models. The oral administration of ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 on mice significantly decreased the amount of scratching, leakage to evans blue, and concentrations of serum immunoglobulin E (IgE) and histamine compared with the atopic dermatitis - induced group. When atopic dermatitis was induced, the transcription factors (GATA-3, retinoic acid-related orphan receptor ${\gamma}$ T [$ROR{\gamma}T$]) and cytokines (interleukin-4 [IL-4], IL-17) of Th2 and Th17 cells were overexpressed at the transcriptional level, and they significantly decreased with oral administration of ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004. In addition, ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 were shown to modulate the immune balance by increasing the expression of Th1 and Treg transcription (T-bet, forkhead box p3 [Foxp3]) and cytokines (interferon-${\gamma}$ [IFN-${\gamma}$], transforming growth factor-${\beta}$ [TGF-${\beta}$]). Galectin-9 and filaggrin were significantly lower in the atopic dermatitis - induced group and significantly higher in the ${\beta}$-1,3/1,6-glucan-treated group. In contrast, thymic stromal lymphopoietin (TSLP) was highest in the atopic dermatitis-induced group, while mice that were orally administered ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 showed similar TSLP levels to the control group. These results indicate that ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 have immunomodulatory effects and atopic dermatitis improvement effects in an animal model of atopic dermatitis. Therefore, it is expected that ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 can be used as natural materials in the treatment of atopic dermatitis.

• Pediatric Infection and Vaccine
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• v.12 no.1
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• pp.75-85
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• 2005

Purpose : Fungal infection is one of the important causes of morbidity and mortality in patients with hematologic malignancies. Amphotericin B(ABV) and itraconazole(ITZA) have been used as the standard empirical antifungal therapy in neutropenic patients with acute leukemia who have persistent fever that does not respond to antibiotic therapy. ABV is an antifungal drug associated with side effects such as fever and chills, symptoms which may be mediated by pro-inflammatory cytokines such as interleukin-$1{\beta}$(IL-$1{\beta}$) and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$). We assessed modulation of these pro-inflammatory cytokines as well as the anti-inflammatory cytokines(IL-4, IL-1Ra) by ABV and ITZA. Methods : From March 2004 to February 2005, a total of 30 episodes from acute leukemia patients with febrile neutropenia were analyzed for this study. They were randomly allocated to receive intravenous ABV or ITZA for 14 days. Clinical responses were evaluated at the completion of therapy, and cytokine IL-$1{\beta}$, TNF-${\alpha}$, IL-4, and IL-1Ra were measured for determination to know the correlation between two antifungal agents and inflammatory cytokines. Results : Empirical antifungal agents were given to 37 patients(ABV 20, ITZA 17), and 30 patients(ABV 15, ITZA 15) were evaluable for efficacy. White blood cell and absolute neutrophil count in the group treated with ITZA increased early days of treatment, so the duration of neutropenia in ITZA group is shorter. Serum creatinine level is lower in ITZA group than in ABV group but this is not statistically significant. There was no significant difference in response rate between two groups. The IL-$1{\beta}$ was increased in ABV treatment group and the ratio of IL-1Ra/IL-$1{\beta}$ is markedly decreased in ABV treatment group while increased in ITZA group. Conclusion : ITZA and ABV have at least equivalent efficacy as empirical antifungal therapy in neutropenic children with acute leukemia. However ITZA is associated with significantly less toxicity in clinical and molecular aspects.