Th2/Th1 switch induced by a single low dose of cyclophosphamide in a rat metastatic lymphoma model
Cyclophosphamide (Cy) is an alkylating agent widely used in cancer chemotherapy. It has a bimodal effect on the immune system, depending on the dose and schedule of administration. We have previously demonstrated that a single low dose of Cy has an antimetastatic effect, achieved through immunomodul...
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| Veröffentlicht in: | Cancer Immunology, Immunotherapy Immunotherapy, 2002-01, Vol.50 (11), p.588-596 |
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| creator | MATAR, Pablo ROZADOS, Viviana R GERVASONI, Silvia I SCHAROVSKY, O. Graciela |
| description | Cyclophosphamide (Cy) is an alkylating agent widely used in cancer chemotherapy. It has a bimodal effect on the immune system, depending on the dose and schedule of administration. We have previously demonstrated that a single low dose of Cy has an antimetastatic effect, achieved through immunomodulation, in lymphoma bearing rats. Such a treatment reduced the splenic production of IL-10, TGF-beta, and NO, restoring the lymphoproliferative capacity. A shift from immunosuppression to immunopotentiation induced by low-dose Cy treatment was mainly mediated by a decrease in IL-10 production. The present study focused on the analysis of the modulation of type-1 cytokine levels by treatment with a single low dose of Cy and the effect these cytokines (IL-2 and IFN-gamma) and IL-10 have on primary tumor and metastatic cell growth. Our results suggest that a single low dose of Cy induces a Th2/Th1 shift in the cytokine profile of lymphoma-bearing rats, which may be responsible for its antimetastatic effect. A direct action of IL-10 as a growth factor and IFN-gamma as a cytotoxic factor on metastatic cells is also shown. |
| doi_str_mv | 10.1007/s00262-001-0237-3 |
| format | Article |
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Graciela</creator><creatorcontrib>MATAR, Pablo ; ROZADOS, Viviana R ; GERVASONI, Silvia I ; SCHAROVSKY, O. Graciela</creatorcontrib><description>Cyclophosphamide (Cy) is an alkylating agent widely used in cancer chemotherapy. It has a bimodal effect on the immune system, depending on the dose and schedule of administration. We have previously demonstrated that a single low dose of Cy has an antimetastatic effect, achieved through immunomodulation, in lymphoma bearing rats. Such a treatment reduced the splenic production of IL-10, TGF-beta, and NO, restoring the lymphoproliferative capacity. A shift from immunosuppression to immunopotentiation induced by low-dose Cy treatment was mainly mediated by a decrease in IL-10 production. The present study focused on the analysis of the modulation of type-1 cytokine levels by treatment with a single low dose of Cy and the effect these cytokines (IL-2 and IFN-gamma) and IL-10 have on primary tumor and metastatic cell growth. Our results suggest that a single low dose of Cy induces a Th2/Th1 shift in the cytokine profile of lymphoma-bearing rats, which may be responsible for its antimetastatic effect. A direct action of IL-10 as a growth factor and IFN-gamma as a cytotoxic factor on metastatic cells is also shown.</description><identifier>ISSN: 0340-7004</identifier><identifier>EISSN: 1432-0851</identifier><identifier>DOI: 10.1007/s00262-001-0237-3</identifier><identifier>PMID: 11807622</identifier><identifier>CODEN: CIIMDN</identifier><language>eng</language><publisher>Berlin: Springer</publisher><subject>Adjuvants, Immunologic - administration & dosage ; Adjuvants, Immunologic - therapeutic use ; Animals ; Antineoplastic agents ; Antineoplastic Agents, Alkylating - administration & dosage ; Antineoplastic Agents, Alkylating - therapeutic use ; Biological and medical sciences ; Cancer therapies ; Chemotherapy ; Cyclophosphamide - administration & dosage ; Cyclophosphamide - therapeutic use ; Cytokines ; Cytotoxicity ; Female ; Immune system ; Interferon-gamma - biosynthesis ; Interferon-gamma - immunology ; Interleukin-10 - biosynthesis ; Interleukin-10 - immunology ; Interleukin-2 - biosynthesis ; Interleukin-2 - immunology ; Lymphatic Metastasis ; Lymphoma ; Lymphoma - drug therapy ; Lymphoma - immunology ; Lymphoma - pathology ; Male ; Medical sciences ; Metastasis ; Original ; Pharmacology. 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Graciela</creatorcontrib><title>Th2/Th1 switch induced by a single low dose of cyclophosphamide in a rat metastatic lymphoma model</title><title>Cancer Immunology, Immunotherapy</title><addtitle>Cancer Immunol Immunother</addtitle><description>Cyclophosphamide (Cy) is an alkylating agent widely used in cancer chemotherapy. It has a bimodal effect on the immune system, depending on the dose and schedule of administration. We have previously demonstrated that a single low dose of Cy has an antimetastatic effect, achieved through immunomodulation, in lymphoma bearing rats. Such a treatment reduced the splenic production of IL-10, TGF-beta, and NO, restoring the lymphoproliferative capacity. A shift from immunosuppression to immunopotentiation induced by low-dose Cy treatment was mainly mediated by a decrease in IL-10 production. The present study focused on the analysis of the modulation of type-1 cytokine levels by treatment with a single low dose of Cy and the effect these cytokines (IL-2 and IFN-gamma) and IL-10 have on primary tumor and metastatic cell growth. Our results suggest that a single low dose of Cy induces a Th2/Th1 shift in the cytokine profile of lymphoma-bearing rats, which may be responsible for its antimetastatic effect. A direct action of IL-10 as a growth factor and IFN-gamma as a cytotoxic factor on metastatic cells is also shown.</description><subject>Adjuvants, Immunologic - administration & dosage</subject><subject>Adjuvants, Immunologic - therapeutic use</subject><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents, Alkylating - administration & dosage</subject><subject>Antineoplastic Agents, Alkylating - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Cancer therapies</subject><subject>Chemotherapy</subject><subject>Cyclophosphamide - administration & dosage</subject><subject>Cyclophosphamide - therapeutic use</subject><subject>Cytokines</subject><subject>Cytotoxicity</subject><subject>Female</subject><subject>Immune system</subject><subject>Interferon-gamma - biosynthesis</subject><subject>Interferon-gamma - immunology</subject><subject>Interleukin-10 - biosynthesis</subject><subject>Interleukin-10 - immunology</subject><subject>Interleukin-2 - biosynthesis</subject><subject>Interleukin-2 - immunology</subject><subject>Lymphatic Metastasis</subject><subject>Lymphoma</subject><subject>Lymphoma - drug therapy</subject><subject>Lymphoma - immunology</subject><subject>Lymphoma - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metastasis</subject><subject>Original</subject><subject>Pharmacology. 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Graciela</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Th2/Th1 switch induced by a single low dose of cyclophosphamide in a rat metastatic lymphoma model</atitle><jtitle>Cancer Immunology, Immunotherapy</jtitle><addtitle>Cancer Immunol Immunother</addtitle><date>2002-01-01</date><risdate>2002</risdate><volume>50</volume><issue>11</issue><spage>588</spage><epage>596</epage><pages>588-596</pages><issn>0340-7004</issn><eissn>1432-0851</eissn><coden>CIIMDN</coden><abstract>Cyclophosphamide (Cy) is an alkylating agent widely used in cancer chemotherapy. It has a bimodal effect on the immune system, depending on the dose and schedule of administration. We have previously demonstrated that a single low dose of Cy has an antimetastatic effect, achieved through immunomodulation, in lymphoma bearing rats. Such a treatment reduced the splenic production of IL-10, TGF-beta, and NO, restoring the lymphoproliferative capacity. A shift from immunosuppression to immunopotentiation induced by low-dose Cy treatment was mainly mediated by a decrease in IL-10 production. The present study focused on the analysis of the modulation of type-1 cytokine levels by treatment with a single low dose of Cy and the effect these cytokines (IL-2 and IFN-gamma) and IL-10 have on primary tumor and metastatic cell growth. Our results suggest that a single low dose of Cy induces a Th2/Th1 shift in the cytokine profile of lymphoma-bearing rats, which may be responsible for its antimetastatic effect. A direct action of IL-10 as a growth factor and IFN-gamma as a cytotoxic factor on metastatic cells is also shown.</abstract><cop>Berlin</cop><pub>Springer</pub><pmid>11807622</pmid><doi>10.1007/s00262-001-0237-3</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer Immunology, Immunotherapy, 2002-01, Vol.50 (11), p.588-596 |
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| subjects | Adjuvants, Immunologic - administration & dosage Adjuvants, Immunologic - therapeutic use Animals Antineoplastic agents Antineoplastic Agents, Alkylating - administration & dosage Antineoplastic Agents, Alkylating - therapeutic use Biological and medical sciences Cancer therapies Chemotherapy Cyclophosphamide - administration & dosage Cyclophosphamide - therapeutic use Cytokines Cytotoxicity Female Immune system Interferon-gamma - biosynthesis Interferon-gamma - immunology Interleukin-10 - biosynthesis Interleukin-10 - immunology Interleukin-2 - biosynthesis Interleukin-2 - immunology Lymphatic Metastasis Lymphoma Lymphoma - drug therapy Lymphoma - immunology Lymphoma - pathology Male Medical sciences Metastasis Original Pharmacology. Drug treatments Rats Spleen Th1 Cells - immunology Th2 Cells - immunology |
| title | Th2/Th1 switch induced by a single low dose of cyclophosphamide in a rat metastatic lymphoma model |
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