Immunotherapy using IL-2 and GM-CSF is a potential treatment for multidrug-resistant Mycobacterium tuberculosis

This study investigated the therapeutic effects of interleukin (IL)-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) co-administrated with antibacterial agents isoniazid (INH) and rifampin (RIF) to treat a mouse model of tuberculo- sis (TB) infection. A drug-susceptible TB strain, H37...

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Veröffentlicht in:Science China. Life sciences 2012-09, Vol.55 (9), p.800-806
Hauptverfasser: Zhang, YongRong, Liu, Jian, Wang, Yong, Xian, QiaoYang, Shao, LingYun, Yang, Zhong, Wang, XiaoNing
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container_issue 9
container_start_page 800
container_title Science China. Life sciences
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creator Zhang, YongRong
Liu, Jian
Wang, Yong
Xian, QiaoYang
Shao, LingYun
Yang, Zhong
Wang, XiaoNing
description This study investigated the therapeutic effects of interleukin (IL)-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) co-administrated with antibacterial agents isoniazid (INH) and rifampin (RIF) to treat a mouse model of tuberculo- sis (TB) infection. A drug-susceptible TB strain, H37Rv was used to infect mice and the effectiveness of IL-2 and GM-CSF was initially evaluated based on survival rate, bacterial counts in lungs and spleens and the pathological condition of the lungs. Next, the therapeutic effect of the immunotherapy regimen was assessed in multidrug-resistant strain OB35-infected mice. In the H37Rv infection model, 1L-2 and GM-CSF monotherapies reduced bacterial numbers in the lungs by 0.82 (P〈0.01) and 0.58 (P〈0.05) lg colony-forming units (CFU), respectively, and in the spleens by 1.42 (P〈0.01) and 1.22 (P〈0.01) lg CFU, re- spectively, compared with the untreated group. Mice receiving immunotherapy developed fewer lesions in the lungs compared with mice receiving antibacterial therapy alone. In the OB35 infection model, immunotherapy with either cytokine resulted in a significant reduction of bacterial load in the lungs and spleens and less severe lesions in the lungs compared with the untreated or antibacterial therapy treated mice. Notably, mice receiving immunotherapy with both cytokines had a 30% survival rate which was higher than that in other treated groups, and had significantly less CFUs in the lungs and spleens (1.02 and 1.34 lg CFU) compared with antibacterial therapy alone (P〈0.01). This study demonstrated that immunotherapy with both IL-2 and GM-CSF may be useful to treat multidrug resistant tuberculosis (MDR-TB).
doi_str_mv 10.1007/s11427-012-4368-x
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A drug-susceptible TB strain, H37Rv was used to infect mice and the effectiveness of IL-2 and GM-CSF was initially evaluated based on survival rate, bacterial counts in lungs and spleens and the pathological condition of the lungs. Next, the therapeutic effect of the immunotherapy regimen was assessed in multidrug-resistant strain OB35-infected mice. In the H37Rv infection model, 1L-2 and GM-CSF monotherapies reduced bacterial numbers in the lungs by 0.82 (P〈0.01) and 0.58 (P〈0.05) lg colony-forming units (CFU), respectively, and in the spleens by 1.42 (P〈0.01) and 1.22 (P〈0.01) lg CFU, re- spectively, compared with the untreated group. Mice receiving immunotherapy developed fewer lesions in the lungs compared with mice receiving antibacterial therapy alone. In the OB35 infection model, immunotherapy with either cytokine resulted in a significant reduction of bacterial load in the lungs and spleens and less severe lesions in the lungs compared with the untreated or antibacterial therapy treated mice. Notably, mice receiving immunotherapy with both cytokines had a 30% survival rate which was higher than that in other treated groups, and had significantly less CFUs in the lungs and spleens (1.02 and 1.34 lg CFU) compared with antibacterial therapy alone (P〈0.01). 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Life sciences</title><addtitle>Sci. China Life Sci</addtitle><addtitle>Sci China Life Sci</addtitle><description>This study investigated the therapeutic effects of interleukin (IL)-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) co-administrated with antibacterial agents isoniazid (INH) and rifampin (RIF) to treat a mouse model of tuberculo- sis (TB) infection. A drug-susceptible TB strain, H37Rv was used to infect mice and the effectiveness of IL-2 and GM-CSF was initially evaluated based on survival rate, bacterial counts in lungs and spleens and the pathological condition of the lungs. Next, the therapeutic effect of the immunotherapy regimen was assessed in multidrug-resistant strain OB35-infected mice. In the H37Rv infection model, 1L-2 and GM-CSF monotherapies reduced bacterial numbers in the lungs by 0.82 (P〈0.01) and 0.58 (P〈0.05) lg colony-forming units (CFU), respectively, and in the spleens by 1.42 (P〈0.01) and 1.22 (P〈0.01) lg CFU, re- spectively, compared with the untreated group. Mice receiving immunotherapy developed fewer lesions in the lungs compared with mice receiving antibacterial therapy alone. In the OB35 infection model, immunotherapy with either cytokine resulted in a significant reduction of bacterial load in the lungs and spleens and less severe lesions in the lungs compared with the untreated or antibacterial therapy treated mice. Notably, mice receiving immunotherapy with both cytokines had a 30% survival rate which was higher than that in other treated groups, and had significantly less CFUs in the lungs and spleens (1.02 and 1.34 lg CFU) compared with antibacterial therapy alone (P〈0.01). This study demonstrated that immunotherapy with both IL-2 and GM-CSF may be useful to treat multidrug resistant tuberculosis (MDR-TB).</description><subject>Animal models</subject><subject>Animals</subject><subject>Antibacterial agents</subject><subject>Antibiotics, Antitubercular - therapeutic use</subject><subject>Biomedical and Life Sciences</subject><subject>Colony-forming cells</subject><subject>Cytokines</subject><subject>Drug resistance</subject><subject>Drug Therapy, Combination</subject><subject>GM-CSF</subject><subject>Granulocyte-macrophage colony-stimulating factor</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use</subject><subject>IL-2</subject><subject>Immunotherapy</subject><subject>Immunotherapy - methods</subject><subject>Infection</subject><subject>Interleukin 2</subject><subject>Interleukin-2 - therapeutic use</subject><subject>Isoniazid</subject><subject>Isoniazid - therapeutic use</subject><subject>Life Sciences</subject><subject>Lung</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Multidrug resistance</subject><subject>Mycobacterium</subject><subject>Mycobacterium tuberculosis</subject><subject>Mycobacterium tuberculosis - drug effects</subject><subject>Research Paper</subject><subject>Rifampin</subject><subject>Rifampin - therapeutic use</subject><subject>Spleen</subject><subject>Survival</subject><subject>Survival Rate</subject><subject>Treatment Outcome</subject><subject>Tuberculosis</subject><subject>Tuberculosis, Multidrug-Resistant - mortality</subject><subject>Tuberculosis, Multidrug-Resistant - therapy</subject><subject>免疫治疗</subject><subject>小鼠模型</subject><subject>巨噬细胞集落刺激因子</subject><subject>抗菌药物</subject><subject>治疗效果</subject><subject>结核分枝杆菌</subject><issn>1674-7305</issn><issn>1869-1889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkUtr3DAUhU1paUKaH9BNUemmG7W6V5IlL8uQx8CELtqujWTLEwfbmugBmX9fDTMJpVCqjXR1v3N0xamq98C-AGPqawQQqCgDpILXmj69qs5B1w0FrZvX5VwrQRVn8qy6jPGBlcU5Q6XeVmfIGUjA5rzy63nOi0_3LpjdnuQ4Lluy3lAkZunJzR1d_bgmYySG7HxySxrNRFJwJs2lIIMPZM5TGvuQtzS4OMZkyv3dvvPWdMmFMc8kZetClydf2u-qN4OZors87RfVr-urn6tbuvl-s15929BOcEhUqp7zhqPVBm2vAIZ6KMM3FrW1EoViQjVcOeADIihjeVcPAIVGLZkw_KL6fPTdBf-YXUztPMbOTZNZnM-xBUCJqATw_6NMQxlK8rqgn_5CH3wOS_nIgWI1g0bqQsGR6oKPMbih3YVxNmFfoPaQXXvMri3ZtYfs2qei-XByznZ2_YviOakC4BGIpbVsXfjz6X-7fjxNcu-X7WPRvRgLjiiVlPw37Ret9w</recordid><startdate>20120901</startdate><enddate>20120901</enddate><creator>Zhang, YongRong</creator><creator>Liu, Jian</creator><creator>Wang, Yong</creator><creator>Xian, QiaoYang</creator><creator>Shao, LingYun</creator><creator>Yang, Zhong</creator><creator>Wang, XiaoNing</creator><general>Science China Press</general><general>Springer Nature B.V</general><scope>2RA</scope><scope>92L</scope><scope>CQIGP</scope><scope>~WA</scope><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7QL</scope><scope>7T5</scope><scope>C1K</scope></search><sort><creationdate>20120901</creationdate><title>Immunotherapy using IL-2 and GM-CSF is a potential treatment for multidrug-resistant Mycobacterium tuberculosis</title><author>Zhang, YongRong ; 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China Life Sci</stitle><addtitle>Sci China Life Sci</addtitle><date>2012-09-01</date><risdate>2012</risdate><volume>55</volume><issue>9</issue><spage>800</spage><epage>806</epage><pages>800-806</pages><issn>1674-7305</issn><eissn>1869-1889</eissn><abstract>This study investigated the therapeutic effects of interleukin (IL)-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) co-administrated with antibacterial agents isoniazid (INH) and rifampin (RIF) to treat a mouse model of tuberculo- sis (TB) infection. A drug-susceptible TB strain, H37Rv was used to infect mice and the effectiveness of IL-2 and GM-CSF was initially evaluated based on survival rate, bacterial counts in lungs and spleens and the pathological condition of the lungs. Next, the therapeutic effect of the immunotherapy regimen was assessed in multidrug-resistant strain OB35-infected mice. In the H37Rv infection model, 1L-2 and GM-CSF monotherapies reduced bacterial numbers in the lungs by 0.82 (P〈0.01) and 0.58 (P〈0.05) lg colony-forming units (CFU), respectively, and in the spleens by 1.42 (P〈0.01) and 1.22 (P〈0.01) lg CFU, re- spectively, compared with the untreated group. Mice receiving immunotherapy developed fewer lesions in the lungs compared with mice receiving antibacterial therapy alone. In the OB35 infection model, immunotherapy with either cytokine resulted in a significant reduction of bacterial load in the lungs and spleens and less severe lesions in the lungs compared with the untreated or antibacterial therapy treated mice. Notably, mice receiving immunotherapy with both cytokines had a 30% survival rate which was higher than that in other treated groups, and had significantly less CFUs in the lungs and spleens (1.02 and 1.34 lg CFU) compared with antibacterial therapy alone (P〈0.01). This study demonstrated that immunotherapy with both IL-2 and GM-CSF may be useful to treat multidrug resistant tuberculosis (MDR-TB).</abstract><cop>Beijing</cop><pub>Science China Press</pub><pmid>23015129</pmid><doi>10.1007/s11427-012-4368-x</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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subjects Animal models
Animals
Antibacterial agents
Antibiotics, Antitubercular - therapeutic use
Biomedical and Life Sciences
Colony-forming cells
Cytokines
Drug resistance
Drug Therapy, Combination
GM-CSF
Granulocyte-macrophage colony-stimulating factor
Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use
IL-2
Immunotherapy
Immunotherapy - methods
Infection
Interleukin 2
Interleukin-2 - therapeutic use
Isoniazid
Isoniazid - therapeutic use
Life Sciences
Lung
Mice
Mice, Inbred C57BL
Multidrug resistance
Mycobacterium
Mycobacterium tuberculosis
Mycobacterium tuberculosis - drug effects
Research Paper
Rifampin
Rifampin - therapeutic use
Spleen
Survival
Survival Rate
Treatment Outcome
Tuberculosis
Tuberculosis, Multidrug-Resistant - mortality
Tuberculosis, Multidrug-Resistant - therapy
免疫治疗
小鼠模型
巨噬细胞集落刺激因子
抗菌药物
治疗效果
结核分枝杆菌
title Immunotherapy using IL-2 and GM-CSF is a potential treatment for multidrug-resistant Mycobacterium tuberculosis
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