• Title/Summary/Keyword: blood cytokine

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Effect of Chlorella vulgaris on Immune-enhancement and Cytokine Production in vivo and in vitro

  • An, Hyo-Jin;Rim, Hong-Kun;Lee, Jong-Hyun;Seo, Min-Jun;Hong, Jin-Woo;Kim, Na-Hyung;Myung, Noh-Yil;Moon, Phil-Dong;Choi, In-Young;Na, Ho-Jeong;Kim, Su-Jin;Jeong, Hyun-Ja;Park, Hyeung-Suk;Han, Jae-Gab;Um, Jae-Young;Hong, Seung-Heon;Kim, Hyung-Min
    • Food Science and Biotechnology
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    • v.17 no.5
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    • pp.953-958
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    • 2008
  • The object of this study was to investigate the immune-enhancing effects of Chlorella vulgaris (CV) on a deteriorated immune function by a protein-energy malnutrition (PEM) diet. Unicellular algae, CV were used as a biological response modifier. Male C57BL/6J mice were fed for 15 days with standard diet or a PEM diet, which is associated with decreased host immune defense. After 8 days, mice in the PEM diet group were orally administered by 0.05, 0.1, and 0.15 g/kg body weight of CV or distilled water. Nutritional parameters, and interferon (IFN)-$\gamma$ levels were significantly increased in the blood serum of the CV (0.15 g/kg)-treated group (29.6$\pm$2.8 pg/mL) compared to the non-treated PEM group (4.1$\pm$0.4 pg/mL, p<0.05). In addition, cell proliferation and production of cytokines were investigated via a CV (0.01, 0.1, and 1 mg/mL) treatment using a human T cell line MOLT-4 cell. The CV treatment (1 mg/mL) significantly increased the production of both IFN-$\gamma$ and interleukin (IL)-2 (51.3$\pm$3.4 and 285.9$\pm$18.8 pg/mL, respectively) compared to the control (51.3$\pm$3.4 and 442.6$\pm$14.3 pg/mL, respectively), but did not affect the production of IL-4. These results suggest that CV may be useful in improving the immune function.

Se 와 Vit. E 투여가 한우 종빈우의 혈액성분과 혈중 Vit. E 농도에 미치는 영향

  • 황환섭;장현용;김정익;정희태;박춘근;김종복;양부근
    • Proceedings of the KSAR Conference
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    • 2002.06a
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    • pp.76-76
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    • 2002
  • 본 연구는 Se과 Vit. E 투여수준이 한우 종빈우 번식효율에 미치는 영향을 규명하기 위하여, 한우 종빈우의 임신말기에 적정량의 Se와 Vit .E를 투여하여, 종빈우의 혈액화학치 변화 및 혈중 Vit. E 농도변화를 규명하였다. 1. 분만 1개월 전 Se 과 Vit. E 투여가 한우 종빈우의 혈액성분에 미치는 영향을 검토한 결과, 평균 혈중 albumin 과 calcium 함량은 각각 투여구가 대조구보다 유의적으로 높았으며 (P<0.05), 평균 혈중 IP 함량은 각각 Se 과 Vit. E 혼합투여구가 여타구보다 높은 성적을 나타냈다 (P<0.05). 그러나 평균 혈중 BUN, creatinine, glucose, cholesterol 및 triglycerides 의 함량은 처리구간 유의적인 차이가 인정되지 않았다 (P>0.05). 2. 분만 2개월 전 Se과 Vit. E 투여가 한우 종빈우의 혈액성분에 미치는 영향을 검토한 결과, 혈중 평균 albumin, BUN, cholesterol, creatinine, glucose, IP, TP, triglycerides 및 Ca 함량은 처리구간 유의적인 차이는 인정되지 않았다 (P>0.05). 3. 한우 종빈우의 분만 l 개월전 Se 및 Vit. E 투여가 한우 종빈우의 혈중 Vit. E 농도에 미치는 영향을 검토한 결과, 평균 혈중 Vit. E 농도는 투여구가 대조구보다 다소 높은 농도를 나타냈으나, 처리구간 유의적인 차이는 인정되지 않았다 (P>0.05). 4. 한우 종빈우에서 분만 2 개월전 Se 및 Vit. E 투여가 혈중 Vit. E 농도에 미치는 영향을 검토한 결과, 평균 혈중 Vit. E 농도는 처리구간 유의적인 차이가 없었으며 (P>0.05), 처리구간 투여횟수의 증가에도 불구하고 혈중 Vit. E 농도는 커다란 차이가 없었다.atform by investigating current and future e-business services platforms involved in domestic and global international banks. Several financial interchange standards which are involved in B2B business of e-procurement, e-placement, e-payment are also investigated.. monocytogenes, E. coli 및 S. enteritidis에 대한 키토산의 최소저해농도는 각각 0.1461 mg/mL, 0.2419 mg/mL, 0.0980 mg/mL 및 0.0490 mg/mL로 측정되었다. 또한 2%(v/v) 초산 자체의 최소저해농도를 측정한 결과, B. cereus, L. mosocytogenes, E. eoli에 대해서는 control과 비교시 유의적인 항균효과는 나타나지 않았다. 반면에 S. enteritidis의 경우는 배양시간 4시간까지는 항균활성을 나타내었지만, 8시간 이후부터는 S. enteritidis의 성장이 control 보다 높아져 배양시간 20시간에서는 control 보다 약 2배 이상 균주의 성장을 촉진시켰다.차에 따른 개별화 학습을 가능하게 할 뿐만 아니라 능동적인 참여를 유도하여 학습효율을 높일 수 있을 것으로 기대된다.향은 패션마케팅의 정의와 적용범위를 축소시킬 수 있는 위험을 내재한 것으로 보여진다. 그런가 하면, 많이 다루어진 주제라 할지라도 개념이나 용어가 통일되지 않고 사용되며 검증되어 통용되는 측정도구의 부재로 인하여 연구결과의 축적이 미비한 상태이다. 따라서, 이에 대한 재고와 새로운 방향 모색이 필요하다고 사료된다.로 사료되며, 임신관련 cytokine에 대한 다양한

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Therapeutic Effects of Probiotics in Patients with Atopic Dermatitis

  • Yim, Jun-Hee;Kim, Duk-Han;Ku, Ja-Kyung;Kang, Yoon-Sung;Kim, Mi-Yeon;Kim, Hyung-Ok;Chung, Myung-Jun;Park, Young-Min
    • Journal of Microbiology and Biotechnology
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    • v.16 no.11
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    • pp.1699-1705
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    • 2006
  • Recent studies have suggested that oral bacteriotherapy with probiotics might be useful for preventing and managing childhood atopic dermatitis (AD). The purpose of this investigation was to evaluate the efficacy and safety of oral treatment with probiotics for adolescent and adult AD patients as well as for childhood AD patients. Sixty-four patients with mild to moderate AD were recruited for treatment with a mixture of four probiotic strains (Lactobacillus rhamnosus, Lactobacillus plantarum, Lactobacillus casei, and Biftdobacterium lactis) twice daily for 8 weeks. The degree of pruritus was determined by a 10-point visual analog scale every other week, and the patients' global assessments of their clinical responses (i.e., better, unchanged, or worse) was done at the end of intervention. The clinical severity of the eczema was evaluated by eczema area and severity index (EASI) score every other week. As laboratory markers, total immunoglobulin E (IgE), eosinophil cationic protein (ECP) in the serum, and cytokine production [interleukin-4 (IL-4), interleukin-10 (IL-10), and $interferon-{\gamma}\;(IFN-{\gamma})$ by the peripheral blood mononuclear cells (PBMCs) were measured at the beginning and at the end of intervention. Of the 64 enrolled AD patients, only 50 patients finally completed the 8-week study. After 8-week treatment with probiotics, the EASI score was significantly improved (p<0.0001), 50% of the patients experienced improvement of their eczema, and significant improvement of the pruritus was also observed (p=0.0002). The effect was more pronounced for the patients with very high IgE levels (>1,000 ku/l) or for the patients with moderate disease severity. There was no significant difference in the therapeutic effects between the childhood AD and adolescent and adult AD patients. There were no significant changes of cytokines, as well as the total IgE and ECP levels, in the patients' serum. Treatment with the mixture of four probiotic strains was generally well tolerated. Our results suggest that the treatment with the mixture of four probiotic strains is beneficial for the management of the adolescent and adult AD patients, as well as for the childhood AD patients.

Fimasartan attenuates renal ischemia-reperfusion injury by modulating inflammation-related apoptosis

  • Cho, Jang-Hee;Choi, Soon-Youn;Ryu, Hye-Myung;Oh, Eun-Joo;Yook, Ju-Min;Ahn, Ji-Sun;Jung, Hee-Yeon;Choi, Ji-Young;Park, Sun-Hee;Kim, Chan-Duck;Kim, Yong-Lim
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.6
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    • pp.661-670
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    • 2018
  • Fimasartan, a new angiotensin II receptor antagonist, reduces myocyte damage and stabilizes atherosclerotic plaque through its anti-inflammatory effect in animal studies. We investigated the protective effects of pretreatment with fimasartan on ischemia-reperfusion injury (IRI) in a mouse model of ischemic renal damage. C57BL/6 mice were pretreated with or without 5 (IR-F5) or 10 (IR-F10) mg/kg/day fimasartan for 3 days. Renal ischemia was induced by clamping bilateral renal vascular pedicles for 30 min. Histology, pro-inflammatory cytokines, and apoptosis assays were evaluated 24 h after IRI. Compared to the untreated group, blood urea nitrogen and serum creatinine levels were significantly lower in the IR-F10 group. IR-F10 kidneys showed less tubular necrosis and interstitial fibrosis than untreated kidneys. The expression of F4/80, a macrophage infiltration marker, and tumor necrosis factor $(TNF)-{\alpha}$, decreased in the IR-F10 group. High-dose fimasartan treatment attenuated the upregulation of $TNF-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 in ischemic kidneys. Fewer TUNEL positive cells were observed in IR-F10 compared to control mice. Fimasartan caused a significant decrease in caspase-3 activity and the level of Bax, and increased the Bcl-2 level. Fimasartan preserved renal function and tubular architecture from IRI in a mouse ischemic renal injury model. Fimasartan also attenuated upregulation of inflammatory cytokines and decreased apoptosis of renal tubular cells. Our results suggest that fimasartan inhibited the process of tubular injury by preventing apoptosis induced by the inflammatory pathway.

Potential Hypersensitivity of Recombinant Mouse IL-2 as a Immunotherapeutic Agent of Cancer in Tumor-bearing BALB/c Mice (항암 면역요법제 인터루킨-2의 면역과민반응 평가연구)

  • Cho, Young-Joo;Eom , Juno H.;Gil , Jung-Hyun;Park , Jae-Hyun;Lee , Jong-Kwon;Oh , Hye-Young;Park , Kui-Lea;Kim , Hyung-Soo
    • YAKHAK HOEJI
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    • v.48 no.6
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    • pp.335-344
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    • 2004
  • Interleukin-2 (IL-2), a glycoprotein mainly secreted by CD4+ T helper Iymphocytes, has been developed to use recombinant cytokine to augment the immune response against cancer since IL-2 not only stimulates T Iymphocytes but also enhances natural killer (NK) cell activity. In order to evaluate the immunological safety of recombinant mouse IL-2 (rmIL-2) in cancer therapy, renal cell carcinoma was established in the flank by s.c. injection of renca cell line. Tumor-bearing BALB/c mice were treated with I.p. injections with $2{\times}10^5$ Lu rmIL-2. Even though the tumor size was diminished, there were not significant recovery of body and relative lymphoid organ weights including thymic atrophy in rmIL-2 immunotherapy. Distribution ratios of T cell subsets in thymus were analysed using flow cytometry. Without regard to dosage of rmIL-2, the ratio of CD3+CD4-CD8- T cells was increased in accordance with survival of solid tumor but that of CD4+CD8+ T cells was decreased dramatically. Emergence of autoantibodies (ANA, anti-dsDNA, and anti-histone) in blood was measured after rmIL-2 treatment. The results showed that the levels of ANA and anti-dsDNA did not significantly changed, but the level of anti-histone was increased significantly owing to rmIL-2 therapy. These results indicate rmIL-2 immunotherapy is to induce the autoimmune potential, and the anti-histone measurement as a biomarker of autoimmunity is useful in cancer immunotherapy.

A Study on the Effect of Herbal-acupuncture with Carthami Flos at Joksamni($ST_{36}$) on Collagen-induced Arthritis in Mice (족삼리(足三里) 홍화약침(紅花藥鍼)처치가 Collagen으로 유발한 생쥐의 관절염 모델에 미치는 영향)

  • Park, Ki-Hong;Lee, Hyun
    • Journal of Acupuncture Research
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    • v.24 no.6
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    • pp.45-61
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    • 2007
  • Objectives : The purpose of this study is to observe the effects of Carthami Flos herbal-acupuncture (CF-HA) at Joksamni($ST_{36}$) on arthritis in mice induced by Collagen II. Methods : The author performed several experimental items, including arthritis evaluation, change in weight, spleen size and stenosis rate, change in cytokine level, IgG, IgM and anti-collagen II, change of immunocyte count and histological change of the CIA mouse joint. Conclusions are as follows: Results : 1. In the CF-HA, the arthritis index and rate and the incidence of arthritis were decreased as the experiment proceeded. 2. In the CF-HA, spleen swell and stenosis, joint edema and change were decreased. 3. In the CF-HA, the level of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ and $IFN-{\gamma}$ in blood serum were significantly decreased. 4. In the CF-HA, the level of IgG, IgM and anti-collagen II were decreased. 5. In the CF- HA, $IFN-{\gamma}$, $IFN-{\gamma}/IL-4$, IL-10 of the culture fluid was decreased. 6. In the CF-HA, the cell rate of $CD3e^+$ and $CD45R^+$, $CD4^+$ and $CD8^+$, $CD4^+/CD25^+$ in spleen was similar to the cell rate of the normal group. 7. In the CF-HA, the cell rate of $CD4^+/CD25^+$, $CD45R^+/CD69^+$ in a lymph node was decreased as in the normal group. 8. In the CF-HA, the cell rate of $CD3^+/CD69^+$, $CD11b^+/Gr-1^+$ in joints was decreased as in the normal group. 9. In the CF-HA, the cartilage destruction and the inflammation cell growth in the H&E stain were decreased. The collagen fiber in the M&T stain were less destructed, therefore the result was similar to the normal group. Conclusions : These results suggest that CH-HA at $ST_{36}$ has an effect in controlling immune reaction and suppressing inflammation in rheumatoid arthritis therefore, the continuous flow of the following study is expected.

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Effects of Mahwangbujaseshin-tang (Mahuangfuzixixintang) (麻黃附子細辛湯) on MIA-Induced Osteoarthritis Rats (마황부자세신탕(麻黃附子細辛湯)이 MIA로 유도된 골관절염 유발 Rat에 미치는 영향)

  • Lee, Hyung-Eun;Oh, Min-Seok
    • Journal of Korean Medicine Rehabilitation
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    • v.24 no.2
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    • pp.65-81
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    • 2014
  • Objectives This study was carried out to find out the anti-osteoarthritic effects of Mahwangbujaseshin- tang (Mahuangfuzixixintang ) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods Osteoarthritis was induced by injecting MIA ($50{\mu}l$) into the knee joint of rats. Rats were divided into a 3 groups (n=7). The injection did not fit the normal group. A week later, after the injection of MIA, while control group took normal saline 2 ml, the extract of Mahwangbujaseshin-tang (Mahuangfuzixixintang ) (MBST) (200 mg/kg) was injected to treated group. After that, we examined hind paw weight bearing ability, functions of liver and kidney, serum TNF-$\alpha$, IL-$1{\beta}$, IL-6, $PGE_2$, $LTB_4$, TIMP-1, MMP-9 and hematology. Volume of cartilage was measured by micro CT arthrography. Injury of synovial tissue was measured by H & E, Safranin-O immunofluorescence. Results 1) DPPH and ABTS free radical scavenging activity of MBST was increased according to concentration of MBST and total phenolic contents were in high level. 2) In RAW 264.7 cells, ROS production was significantly decreased in MBST (at 10, $100{\mu}g/ml$) and NO was also decreased but meaningless in MBST (at $100{\mu}g/ml$). 3) In RAW 264.7 cells, IL-6 production was significantly decreased in MBST (at $100{\mu}g/ml$) and TNF-$\alpha$ and IL-$1{\beta}$ production were also decreased but meaningless in MBST (at $100{\mu}g/ml$). 4) In hind legs weight-bearing measurement, level of weight-bearing was increased. 5) Functions of liver and kidney were not affected. 6) TNF-$\alpha$, IL-$1{\beta}$, IL-6, $PGE_2$, $LTB_4$, MMP-9 and TIMP-1 production were significantly decreased. 7) In hematology, the levels of neutrophils, monocytes were significantly decreased and the levels of white blood cells, lymphocytes were also decreased but meaningless. 8) In micro CT-arthrography, cartilage volume was significantly increased. 9) Histopathologically, injury on cartilage and synovial membrane of MBST group was decreased. Conclusions Based on all results mentioned above, Mahwangbujaseshin-tang (Mahuangfuzixixintang) is believed to be meaningful for suppressing the progress of osteoarthritis. And it is related to inhibiting the activity of inflammatory cytokine and injury of volume in cartilage.

Prognostic and Predictive Value of Hematologic Parameters in Patients with Metastatic Renal Cell Carcinoma: Second Line Sunitinib Treatment Following IFN-alpha

  • Dirican, Ahmet;Kucukzeybek, Yuksel;Erten, Cigdem;Somali, Isil;Demir, Lutfiye;Can, Alper;Payzin, Kadriye Bahriye;Bayoglu, Ibrahim Vedat;Akyol, Murat;Yildiz, Yasar;Koseoglu, Mehmet;Alacacioglu, Ahmet;Tarhan, Mustafa Oktay
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.3
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    • pp.2101-2105
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    • 2013
  • Background: Long-term survival is a problem with locally advanced and metastatic renal cell carcinomas. Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor, but data on sunitinib use as a second line treatment in metastatic renal cell carcinoma (mRCC) are limited. Prognostic and predictive value of peripheral blood markers has been shown for many cancers. Materials and Methods: Efficacy and safety profiles of sunitinib after interferon alpha (IFN-${\alpha}$) were evaluated based on retrospective data for 23 patients with mRCC. Hematological parameters (neutrophils, lymphocytes, platelets, mean platelet volume, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio) were recorded at the time of metastasis. It was evaluated whether hematological parameters were prognostic and predictive factors. Results: Median progression-free survival (PFS) time was 16.5 months (95%CI: 0-34.5). Median overall survival (OS) time was 25.7 months (95%CI: 10.8-40.0). Most common side effects were neutropenia (52.2%), stomatitis (26.1%) and hand-food syndrome (26.1%). PFS was found 3.13 vs 17.1 months in patients with neutrophil / lymphocyte ratio (NLR)>3 vs $NLR{\leq}3$ (p:0.012). Median OS was 6.96 vs 27.1 months in patients with NLR>3 vs $NLR{\leq}3$ (p:0.001).While 75% of patients who responded to sunitinib had $NLR{\leq}3$, in 72% of patients with no response to sunitinib NLR>3 was detected (p:0.036). The association between the Memorial Sloan-Kettering Cancer Center (MSKCC) criteria and NLR was statistically significant (p:0.022). Conclusions: Data on second line sunitinib treatment following cytokine in mRCC are limited. In our study, we observed second line sunitinib treatment following IFN-${\alpha}$ to be effective and tolerable. NLRappeared to have prognostic and predictive value.

Risk of the Gastric Cancer Associated with the Interleukin $1\beta$ Gene Polymorphism and Helicobacter pylori (Helicobacter pylori 감염과 Interleukin $1\beta$ 유전자의 다형성에 따른 위암 발생 위험도)

  • Park, Sang-Hyub;Song-Kyo-Young;Kim, Jin-Jo;Jin-Hyung-Min;Kim, Wook;Park, Cho-Hyun;Park, Seung-Man;Lim-Keun-Woo;Park, Woo-Bae;Kim, Seung-Nam;Jeon, Hae-Myung
    • Journal of Gastric Cancer
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    • v.4 no.3
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    • pp.149-155
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    • 2004
  • Purpose: According to the recent studies, it is shown that the polymorphism of Interleukin $1\beta$ gene is associated with the incidence of gastric cancer caused by the Helicobacter pylori infection. Interleukin $1\beta$ is a cytokine markedly inhibiting gastric acid secretion. Interleukin $1\beta$ production associated with Helicobacter pylori gastric infection may exacerbate mucosal damage including chronic gastritis and atrophic gastritis, may induce eventual neoplasia. Among these Interleukin $1\beta$ gene polymorphisms, polymorphisms at -31 portion and -511 portion may associated with these processes, eventually increase the risk of gastric cancer. We investigated the risk of gastric cancer according to the Helicobacter pylori infection and genetic polymorphism of Interleukin $1\beta$ in gastric cancer patients. Materials and Methods: 176 individuals with gastric cancer and 40 healthy controls were analyzed. Each group was divided into two groups whether they infected with Helicobacter pylori or not. DNA was extracted from the peripheral blood in all groups. The PCR-RFLP method was used for investigating the distribution of genotype of C/C, C/T, T/T at -31 portion and -511 portion. Results: T/T genotype at -511 portion was $19.3\%$ in gastric cancer cases and $10\%$ in controls, which was statistically significant. (P=0.0432) The risk of gastric cancer was increased 4.86 ($1.26\∼18.77$) in group which had T/T genotype. In gastric cancer cases, C/C genotype at 31 portion was $27.6\%$ in group with Helicobacter pylori infection and $12.8\%$ in group without infection, which was statistically significant. (P=0.0047) The risk of gastric cancer was increased 4.82 ($1.81\~12.81$) in group which had C/C genotype. Conclusion: T genotype at -511 portion among the Interleukin $1\beta$ genetic polymorphisms may be the risk factor of gastric cancer. And, with Helicobacter pylori infection, C genotype at -31 portion may be the risk factor of gastric cancer.

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Relationship between Endotoxin Level of in Swine Farm Dust and Cellular Immunity of Husbandry Workers (돈사 분진 함유 내독소 수준과 축사 작업자들의 세포면역력간 상관성 분석)

  • Kim, Hyoung Ah;Kim, Ji Youn;Shin, Kyeong Min;Jo, Ji Hoon;Roque, Katharine;Jo, Gwang Ho;Heo, Yong
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.23 no.4
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    • pp.393-401
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    • 2013
  • Objectives: Endotoxins in dust generated in occupational settings is known to contribute to the occurrence of respiratory illness among workers. The relationship between the level of endotoxins in total dust or respirable particulates collected from swine farms and immunological markers related with respiratory allergy was evaluated among swine husbandry workers. Materials and Methods: Peripheral blood samples were collected from ten workers at ten swine farms at Gyeonggi province, Korea. Peripheral mononuclear cells were stimulated with phorbol 12-myristate 13-acetate and ionomycin for 48 hours. The levels of various cytokines produced at culture supernatants were determined using a commercially available ELISA kit. The concentration of particulate matter($PM_{10}$) in the indoor air of the swine farms was evaluated using a PVC membrane filter and mini volume air sampler, and endotoxin levels in the dust were measured by Limulus Amebocyte Lysate Kinetic QCL method. Results: Levels of endotoxins in the total dust were categorized into high(geometric mean: $109.35EU/m^3$) and low concentrations (geometric mean: $0.95EU/m^3$) for five swine farms. Interleukin-4 levels were higher in the high endotoxin group than in the low endotoxin group, while interferon-${\gamma}$ levels were lower in the high endotoxin group than in the low endotoxin group. The ratio (interferon-${\gamma}$ to interleukin-4), indicating immunologic skewedness against allergic reactivities, was lower in the high endotoxin group($1.15{\pm}0.60$) than the low endotoxin group($3.09{\pm}2.38$). In addition, the level of interleukin-13, another cytokine contributing to the occurrence of allergic responses, was significantly higher in the at the high endotoxin group($1.12{\pm}0.37ng/m{\ell}$) than in the low endotoxin group($0.37{\pm}0.04ng/m{\ell}$). Hematologic assessment showed significantly lower cellularity in the number of total leukocytes, neutrophils, and eosinophils in the high endotoxin group than in the low endotoxin group. Conclusions: Even though a sufficient number of swine workers and farms were not investigated, this study generlly suggests that the immunological function of swine farm workers exposed to high levels of endotoxin could be modulated toward allergic reactivities.