Mizoribine provides effective treatment of sequential histological change of arteritis and reduction of inflammatory cytokines and chemokines in an animal model of Kawasaki disease
<p>Abstract</p> <p>Background</p> <p>Intravenous immunoglobulin (IVIg) treatment results in an effective response from patients with acute-phase Kawasaki disease (KD), but 16.5% of them remain nonresponsive to IVIg. To address this therapeutic challenge, we tried a new...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-09-01
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| Series: | Pediatric Rheumatology Online Journal |
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| Online Access: | http://www.ped-rheum.com/content/9/1/30 |
| _version_ | 1818758574289977344 |
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| author | Ohno Naohito Nagi-Miura Noriko Yamada Hitomi Yokouchi Yuki Nagao Tomokazu Oharaseki Toshiaki Takahashi Kei Saji Tsutomu Okazaki Tomio Suzuki Kazuo |
| author_facet | Ohno Naohito Nagi-Miura Noriko Yamada Hitomi Yokouchi Yuki Nagao Tomokazu Oharaseki Toshiaki Takahashi Kei Saji Tsutomu Okazaki Tomio Suzuki Kazuo |
| author_sort | Ohno Naohito |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Intravenous immunoglobulin (IVIg) treatment results in an effective response from patients with acute-phase Kawasaki disease (KD), but 16.5% of them remain nonresponsive to IVIg. To address this therapeutic challenge, we tried a new therapeutic drug, mizoribine (MZR), in a mouse model of KD, which we have established using injections of <it>Candida albicans </it>water-soluble fractions (CAWS).</p> <p>Methods</p> <p>CAWS (4 mg/mouse) were injected intraperitoneally into C57BL/6N mice for 5 consecutive days. MZR or IgG was administered for 5 days. After 4 weeks, the mice were sacrificed and autopsied, the hearts were fixed in 10% neutral formalin, and plasma was taken to measure cytokines and chemokines using the Bio-Plex system.</p> <p>The incidence of panvasculitis in the coronary arteries and aortic root was 100% in the control group. The incidence of panvasculitis in the MZR group decreased to 50%. Moreover, the scope and severity of the inflammation of those sites were significantly reduced in the MZR group as well as the IgG group. On the other hand, increased cytokines and chemokines, such as IL-1α, TNF-α, KC, MIP-1α, GM-CSF, and IL-13, in the nontreatment group were significantly suppressed by treatment with MZR, but the MCP-1 level increased. In addition, IL-1α, TNF-α, IL-10, IL-13, and MIP-1α were suppressed by treatment in the IgG group.</p> <p>Results</p> <p>The incidence of panvasculitis in the coronary arteries and aortic root was 100% in the control group. The incidence of panvasculitis in the MZR group decreased to 50%. Moreover, the scope and severity of the inflammation of those sites were significantly reduced in the MZR group as well as the IgG group. On the other hand, increased cytokines and chemokines, such as IL-1α TNF-α, KC, MIP-1α, GM-CSF, and IL-13, in the nontreatment group were significantly suppressed by treatment with MZR, but the MCP-1 level increased. In addition, IL-1α, TNF-α, IL-10, IL-13, and MIP-1α were suppressed by treatment in the IgG group.</p> <p>Conclusion</p> <p>MZR treatment suppressed not only the incidence, range, and degree of vasculitis, but also inflammatory cytokines and chemokines in the plasma of the KD vasculitis model mice, suggesting that MZR may be useful for treatment of KD.</p> |
| first_indexed | 2024-12-18T06:29:00Z |
| format | Article |
| id | doaj.art-a71bfde0f76b4f66970ce3bf2caa9a6b |
| institution | Directory Open Access Journal |
| issn | 1546-0096 |
| language | English |
| last_indexed | 2024-12-18T06:29:00Z |
| publishDate | 2011-09-01 |
| publisher | BMC |
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| series | Pediatric Rheumatology Online Journal |
| spelling | doaj.art-a71bfde0f76b4f66970ce3bf2caa9a6b2022-12-21T21:17:58ZengBMCPediatric Rheumatology Online Journal1546-00962011-09-01913010.1186/1546-0096-9-30Mizoribine provides effective treatment of sequential histological change of arteritis and reduction of inflammatory cytokines and chemokines in an animal model of Kawasaki diseaseOhno NaohitoNagi-Miura NorikoYamada HitomiYokouchi YukiNagao TomokazuOharaseki ToshiakiTakahashi KeiSaji TsutomuOkazaki TomioSuzuki Kazuo<p>Abstract</p> <p>Background</p> <p>Intravenous immunoglobulin (IVIg) treatment results in an effective response from patients with acute-phase Kawasaki disease (KD), but 16.5% of them remain nonresponsive to IVIg. To address this therapeutic challenge, we tried a new therapeutic drug, mizoribine (MZR), in a mouse model of KD, which we have established using injections of <it>Candida albicans </it>water-soluble fractions (CAWS).</p> <p>Methods</p> <p>CAWS (4 mg/mouse) were injected intraperitoneally into C57BL/6N mice for 5 consecutive days. MZR or IgG was administered for 5 days. After 4 weeks, the mice were sacrificed and autopsied, the hearts were fixed in 10% neutral formalin, and plasma was taken to measure cytokines and chemokines using the Bio-Plex system.</p> <p>The incidence of panvasculitis in the coronary arteries and aortic root was 100% in the control group. The incidence of panvasculitis in the MZR group decreased to 50%. Moreover, the scope and severity of the inflammation of those sites were significantly reduced in the MZR group as well as the IgG group. On the other hand, increased cytokines and chemokines, such as IL-1α, TNF-α, KC, MIP-1α, GM-CSF, and IL-13, in the nontreatment group were significantly suppressed by treatment with MZR, but the MCP-1 level increased. In addition, IL-1α, TNF-α, IL-10, IL-13, and MIP-1α were suppressed by treatment in the IgG group.</p> <p>Results</p> <p>The incidence of panvasculitis in the coronary arteries and aortic root was 100% in the control group. The incidence of panvasculitis in the MZR group decreased to 50%. Moreover, the scope and severity of the inflammation of those sites were significantly reduced in the MZR group as well as the IgG group. On the other hand, increased cytokines and chemokines, such as IL-1α TNF-α, KC, MIP-1α, GM-CSF, and IL-13, in the nontreatment group were significantly suppressed by treatment with MZR, but the MCP-1 level increased. In addition, IL-1α, TNF-α, IL-10, IL-13, and MIP-1α were suppressed by treatment in the IgG group.</p> <p>Conclusion</p> <p>MZR treatment suppressed not only the incidence, range, and degree of vasculitis, but also inflammatory cytokines and chemokines in the plasma of the KD vasculitis model mice, suggesting that MZR may be useful for treatment of KD.</p>http://www.ped-rheum.com/content/9/1/30Kawasaki diseasean animal modelIVIgcoronary arteritisinflammatory cytokines and chemokinesmizoribine |
| spellingShingle | Ohno Naohito Nagi-Miura Noriko Yamada Hitomi Yokouchi Yuki Nagao Tomokazu Oharaseki Toshiaki Takahashi Kei Saji Tsutomu Okazaki Tomio Suzuki Kazuo Mizoribine provides effective treatment of sequential histological change of arteritis and reduction of inflammatory cytokines and chemokines in an animal model of Kawasaki disease Pediatric Rheumatology Online Journal Kawasaki disease an animal model IVIg coronary arteritis inflammatory cytokines and chemokines mizoribine |
| title | Mizoribine provides effective treatment of sequential histological change of arteritis and reduction of inflammatory cytokines and chemokines in an animal model of Kawasaki disease |
| title_full | Mizoribine provides effective treatment of sequential histological change of arteritis and reduction of inflammatory cytokines and chemokines in an animal model of Kawasaki disease |
| title_fullStr | Mizoribine provides effective treatment of sequential histological change of arteritis and reduction of inflammatory cytokines and chemokines in an animal model of Kawasaki disease |
| title_full_unstemmed | Mizoribine provides effective treatment of sequential histological change of arteritis and reduction of inflammatory cytokines and chemokines in an animal model of Kawasaki disease |
| title_short | Mizoribine provides effective treatment of sequential histological change of arteritis and reduction of inflammatory cytokines and chemokines in an animal model of Kawasaki disease |
| title_sort | mizoribine provides effective treatment of sequential histological change of arteritis and reduction of inflammatory cytokines and chemokines in an animal model of kawasaki disease |
| topic | Kawasaki disease an animal model IVIg coronary arteritis inflammatory cytokines and chemokines mizoribine |
| url | http://www.ped-rheum.com/content/9/1/30 |
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