Use of immunostimulatory liposome-nucleic acid complexes in allergen-specific immunotherapy of dogs with refractory atopic dermatitis -- a pilot study

This pilot study evaluated the effects of immunostimulatory liposome-plasmid-DNA complexes combined with specific allergens for immunotherapy of refractory canine atopic dermatitis. Seven dogs with previously diagnosed atopic dermatitis and unsatisfactory response to at least 12 months of convention...

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Veröffentlicht in:Veterinary dermatology 2005-02, Vol.16 (1), p.61-68
Hauptverfasser: Mueler, R.S, Veir, J, Fieseler, K.V, Dow, S.W
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creator Mueler, R.S
Veir, J
Fieseler, K.V
Dow, S.W
description This pilot study evaluated the effects of immunostimulatory liposome-plasmid-DNA complexes combined with specific allergens for immunotherapy of refractory canine atopic dermatitis. Seven dogs with previously diagnosed atopic dermatitis and unsatisfactory response to at least 12 months of conventional allergen-specific immunotherapy underwent a series of six intradermal injections (weeks 0, 2, 4, 6, 10 and 14), with patient-specific allergen extracts contained in cationic liposome-DNA complexes. Degree of pruritus was assessed on a visual analogue scale. Lesion scores were determined using the Canine Atopic Dermatitis Extent and Severity Index (CADESI) and medication usage was recorded at weeks 0 and 14. Canine cytokine mRNA expression in peripheral blood mononuclear cells collected prior to treatment and at the completion of the study was determined for IFN-gamma, IL-4, TNF and IL-10 genes using quantitative reverse transcription competitive polymerase chain reaction. Repeated intradermal injections of specific allergens incorporated into liposome-nucleic acid complexes were well tolerated in all seven dogs. There was a significant improvement in pruritus scores (P = 0.0277) and concurrent significant decrease in IL-4 production (P = 0.0428) at the completion of the trial compared to pretreatment values. Medication scores, CADESI and production of other cytokines did not change significantly with treatment. These early results suggest that antigen-specific immunotherapy using a novel liposome-nucleic acid complex vaccine may be beneficial for treatment of established atopic dermatitis in dogs using lower antigen doses. Further investigations in larger numbers of dogs with earlier stages of disease are warranted.
doi_str_mv 10.1111/j.1365-3164.2005.00426.x
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Seven dogs with previously diagnosed atopic dermatitis and unsatisfactory response to at least 12 months of conventional allergen-specific immunotherapy underwent a series of six intradermal injections (weeks 0, 2, 4, 6, 10 and 14), with patient-specific allergen extracts contained in cationic liposome-DNA complexes. Degree of pruritus was assessed on a visual analogue scale. Lesion scores were determined using the Canine Atopic Dermatitis Extent and Severity Index (CADESI) and medication usage was recorded at weeks 0 and 14. Canine cytokine mRNA expression in peripheral blood mononuclear cells collected prior to treatment and at the completion of the study was determined for IFN-gamma, IL-4, TNF and IL-10 genes using quantitative reverse transcription competitive polymerase chain reaction. Repeated intradermal injections of specific allergens incorporated into liposome-nucleic acid complexes were well tolerated in all seven dogs. There was a significant improvement in pruritus scores (P = 0.0277) and concurrent significant decrease in IL-4 production (P = 0.0428) at the completion of the trial compared to pretreatment values. Medication scores, CADESI and production of other cytokines did not change significantly with treatment. These early results suggest that antigen-specific immunotherapy using a novel liposome-nucleic acid complex vaccine may be beneficial for treatment of established atopic dermatitis in dogs using lower antigen doses. 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Seven dogs with previously diagnosed atopic dermatitis and unsatisfactory response to at least 12 months of conventional allergen-specific immunotherapy underwent a series of six intradermal injections (weeks 0, 2, 4, 6, 10 and 14), with patient-specific allergen extracts contained in cationic liposome-DNA complexes. Degree of pruritus was assessed on a visual analogue scale. Lesion scores were determined using the Canine Atopic Dermatitis Extent and Severity Index (CADESI) and medication usage was recorded at weeks 0 and 14. Canine cytokine mRNA expression in peripheral blood mononuclear cells collected prior to treatment and at the completion of the study was determined for IFN-gamma, IL-4, TNF and IL-10 genes using quantitative reverse transcription competitive polymerase chain reaction. Repeated intradermal injections of specific allergens incorporated into liposome-nucleic acid complexes were well tolerated in all seven dogs. There was a significant improvement in pruritus scores (P = 0.0277) and concurrent significant decrease in IL-4 production (P = 0.0428) at the completion of the trial compared to pretreatment values. Medication scores, CADESI and production of other cytokines did not change significantly with treatment. These early results suggest that antigen-specific immunotherapy using a novel liposome-nucleic acid complex vaccine may be beneficial for treatment of established atopic dermatitis in dogs using lower antigen doses. 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dosage</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Injections, Intradermal - veterinary</subject><subject>Interferon-gamma - biosynthesis</subject><subject>Interferon-gamma - genetics</subject><subject>Interferon-gamma - immunology</subject><subject>interferons</subject><subject>interleukin-10</subject><subject>Interleukin-10 - biosynthesis</subject><subject>Interleukin-10 - genetics</subject><subject>Interleukin-10 - immunology</subject><subject>interleukin-4</subject><subject>Interleukin-4 - biosynthesis</subject><subject>Interleukin-4 - genetics</subject><subject>Interleukin-4 - immunology</subject><subject>lesions (animal)</subject><subject>Leukocytes, Mononuclear - immunology</subject><subject>Liposomes</subject><subject>liposomes (artificial)</subject><subject>messenger RNA</subject><subject>monocytes</subject><subject>Pilot Projects</subject><subject>plasmids</subject><subject>pruritus</subject><subject>Pruritus - pathology</subject><subject>Pruritus - therapy</subject><subject>Pruritus - veterinary</subject><subject>Reverse Transcriptase Polymerase Chain Reaction - veterinary</subject><subject>RNA, Messenger - biosynthesis</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - immunology</subject><subject>Severity of Illness Index</subject><subject>Treatment Outcome</subject><subject>Tumor Necrosis Factor-alpha - biosynthesis</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><subject>Tumor Necrosis Factor-alpha - immunology</subject><subject>tumor necrosis factors</subject><subject>vaccination</subject><subject>vaccine development</subject><subject>Vaccines - immunology</subject><issn>0959-4493</issn><issn>1365-3164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1u1DAUhSMEokPhFcArWCVcxz-JJTZo2imgAosysLQ8jjP14IyDnaiTF-F58TSjskN4Y0v-zjm-PlmGMBQ4rbe7AhPOcoI5LUoAVgDQkheHR9ni4eJxtgDBRE6pIGfZsxh3AFAJQZ5mZ5hVJcNQLbLf62iQb5HtunHv42C70anBhwk52_voO5PvR-2M1Uhp2yDtu96Zg4nI7pFyzoSt2eexN9q2iZlthlsTVD8dfRu_jejODrcomDYofW-dAvoENyZ0arCDjSjPkUK9dX5AcRib6Xn2pFUumhen_Txbry6_LT_k11-vPi7fX-eacuB5VROOoRYMdNOWm03TcM40E20NnNaKAOYN6HJjSlzXVUnT1C3btECFpqLWNTnP3sy-ffC_RhMH2dmojXNqb_wYZZVioOJEJPL1P0le0fSjgiWwnkEdfIxpatkH26kwSQzy2J7cyWNJ8liSPLYn79uThyR9ecoYN51p_gpPdSXg3QzcWWem_zaW3y8u0yHJ81lu42AOD3IVfqbnk4rJH1-u5MUNXq4-V5_kKvGvZr5VXqptsFGub0rABEAIoDUlfwBCDML0</recordid><startdate>200502</startdate><enddate>200502</enddate><creator>Mueler, R.S</creator><creator>Veir, J</creator><creator>Fieseler, K.V</creator><creator>Dow, S.W</creator><general>Blackwell Science Ltd</general><scope>FBQ</scope><scope>BSCLL</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>7X8</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>200502</creationdate><title>Use of immunostimulatory liposome-nucleic acid complexes in allergen-specific immunotherapy of dogs with refractory atopic dermatitis -- a pilot study</title><author>Mueler, R.S ; 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dosage</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Injections, Intradermal - veterinary</topic><topic>Interferon-gamma - biosynthesis</topic><topic>Interferon-gamma - genetics</topic><topic>Interferon-gamma - immunology</topic><topic>interferons</topic><topic>interleukin-10</topic><topic>Interleukin-10 - biosynthesis</topic><topic>Interleukin-10 - genetics</topic><topic>Interleukin-10 - immunology</topic><topic>interleukin-4</topic><topic>Interleukin-4 - biosynthesis</topic><topic>Interleukin-4 - genetics</topic><topic>Interleukin-4 - immunology</topic><topic>lesions (animal)</topic><topic>Leukocytes, Mononuclear - immunology</topic><topic>Liposomes</topic><topic>liposomes (artificial)</topic><topic>messenger RNA</topic><topic>monocytes</topic><topic>Pilot Projects</topic><topic>plasmids</topic><topic>pruritus</topic><topic>Pruritus - pathology</topic><topic>Pruritus - therapy</topic><topic>Pruritus - veterinary</topic><topic>Reverse Transcriptase Polymerase Chain Reaction - veterinary</topic><topic>RNA, Messenger - biosynthesis</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - immunology</topic><topic>Severity of Illness Index</topic><topic>Treatment Outcome</topic><topic>Tumor Necrosis Factor-alpha - biosynthesis</topic><topic>Tumor Necrosis Factor-alpha - genetics</topic><topic>Tumor Necrosis Factor-alpha - immunology</topic><topic>tumor necrosis factors</topic><topic>vaccination</topic><topic>vaccine development</topic><topic>Vaccines - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mueler, R.S</creatorcontrib><creatorcontrib>Veir, J</creatorcontrib><creatorcontrib>Fieseler, K.V</creatorcontrib><creatorcontrib>Dow, S.W</creatorcontrib><collection>AGRIS</collection><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Veterinary dermatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mueler, R.S</au><au>Veir, J</au><au>Fieseler, K.V</au><au>Dow, S.W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Use of immunostimulatory liposome-nucleic acid complexes in allergen-specific immunotherapy of dogs with refractory atopic dermatitis -- a pilot study</atitle><jtitle>Veterinary dermatology</jtitle><addtitle>Vet Dermatol</addtitle><date>2005-02</date><risdate>2005</risdate><volume>16</volume><issue>1</issue><spage>61</spage><epage>68</epage><pages>61-68</pages><issn>0959-4493</issn><eissn>1365-3164</eissn><abstract>This pilot study evaluated the effects of immunostimulatory liposome-plasmid-DNA complexes combined with specific allergens for immunotherapy of refractory canine atopic dermatitis. Seven dogs with previously diagnosed atopic dermatitis and unsatisfactory response to at least 12 months of conventional allergen-specific immunotherapy underwent a series of six intradermal injections (weeks 0, 2, 4, 6, 10 and 14), with patient-specific allergen extracts contained in cationic liposome-DNA complexes. Degree of pruritus was assessed on a visual analogue scale. Lesion scores were determined using the Canine Atopic Dermatitis Extent and Severity Index (CADESI) and medication usage was recorded at weeks 0 and 14. Canine cytokine mRNA expression in peripheral blood mononuclear cells collected prior to treatment and at the completion of the study was determined for IFN-gamma, IL-4, TNF and IL-10 genes using quantitative reverse transcription competitive polymerase chain reaction. Repeated intradermal injections of specific allergens incorporated into liposome-nucleic acid complexes were well tolerated in all seven dogs. There was a significant improvement in pruritus scores (P = 0.0277) and concurrent significant decrease in IL-4 production (P = 0.0428) at the completion of the trial compared to pretreatment values. Medication scores, CADESI and production of other cytokines did not change significantly with treatment. These early results suggest that antigen-specific immunotherapy using a novel liposome-nucleic acid complex vaccine may be beneficial for treatment of established atopic dermatitis in dogs using lower antigen doses. Further investigations in larger numbers of dogs with earlier stages of disease are warranted.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>15725107</pmid><doi>10.1111/j.1365-3164.2005.00426.x</doi><tpages>8</tpages></addata></record>
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subjects Adjuvants, Immunologic - administration & dosage
allergens
Allergens - administration & dosage
Allergens - therapeutic use
Animals
atopic dermatitis
cytokines
Dermatitis, Atopic - immunology
Dermatitis, Atopic - pathology
Dermatitis, Atopic - therapy
Dermatitis, Atopic - veterinary
Desensitization, Immunologic - methods
Desensitization, Immunologic - veterinary
disease severity
DNA
dog diseases
Dog Diseases - immunology
Dog Diseases - pathology
Dog Diseases - therapy
Dogs
Dose-Response Relationship, Immunologic
Gene Expression Regulation
immunostimulants
Immunosuppressive Agents - administration & dosage
Immunosuppressive Agents - therapeutic use
Injections, Intradermal - veterinary
Interferon-gamma - biosynthesis
Interferon-gamma - genetics
Interferon-gamma - immunology
interferons
interleukin-10
Interleukin-10 - biosynthesis
Interleukin-10 - genetics
Interleukin-10 - immunology
interleukin-4
Interleukin-4 - biosynthesis
Interleukin-4 - genetics
Interleukin-4 - immunology
lesions (animal)
Leukocytes, Mononuclear - immunology
Liposomes
liposomes (artificial)
messenger RNA
monocytes
Pilot Projects
plasmids
pruritus
Pruritus - pathology
Pruritus - therapy
Pruritus - veterinary
Reverse Transcriptase Polymerase Chain Reaction - veterinary
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
RNA, Messenger - immunology
Severity of Illness Index
Treatment Outcome
Tumor Necrosis Factor-alpha - biosynthesis
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - immunology
tumor necrosis factors
vaccination
vaccine development
Vaccines - immunology
title Use of immunostimulatory liposome-nucleic acid complexes in allergen-specific immunotherapy of dogs with refractory atopic dermatitis -- a pilot study
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