| A combination therapy using IL-12 and soluble IL-4 receptor on herpes simplex virus Type 1 infection in a human-SCID chimera model of thermal injury. | |
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MedLine Citation:
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PMID: 12498818 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Herpes simplex virus type 1 (HSV-1) is a severe pathogen in thermally injured patients. Type 1 T cells are essential for the host's anti-HSV protective immunity. Type 2 cytokines, commonly detected in thermally injured patients, have been described as inhibitors for the type 1 T cell generation. Therefore, the antiviral effects of combination therapy with a type 1 T cell inducer [interleukin (IL)-12] and a type 2 T cell inhibitor [soluble IL-4 receptor (sIL-4R)] were investigated in severe combined immunodeficiency (SCID) mice inoculated with peripheral blood lymphocytes (PBL) of thermally injured patients. Patient PBL-SCID chimeras (SCID mice inoculated with patient PBL) were susceptible to infection with 1 x 10(3) PFU/kg of HSV-1 (0% survival), while healthy PBL-SCID chimeras (SCID mice inoculated with PBL from healthy donors) were resistant (92% survival). When patient PBL-SCID chimeras exposed to HSV-1 were treated with saline, human recombinant (r) IL-12 or human sIL-4R, 0, 0, or 12.5% of them survived, respectively. However, 75% of these chimeras survived when they were treated with rIL-12 and sIL-4R in combination. These results indicate that HSV-1 infection in patient PBL-SCID chimeras was therapeutically controlled by the inducer of type 1 T cell responses and the inhibitor of type 2 T cell responses in combination. |
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Authors:
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Tatsushi Katakura; Makiko Kobayashi; Kazuhiko Fujita; David N Herndon; Richard B Pollard; Fujio Suzuki |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Clinical immunology (Orlando, Fla.) Volume: 105 ISSN: 1521-6616 ISO Abbreviation: Clin. Immunol. Publication Date: 2002 Dec |
Date Detail:
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Created Date: 2002-12-24 Completed Date: 2003-02-03 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 100883537 Medline TA: Clin Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 363-70 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Burns / complications* Chimera Drug Therapy, Combination Herpes Simplex / complications, drug therapy* Herpesvirus 1, Human* Humans Interleukin-12 / therapeutic use* Lymphocytes Male Mice Mice, SCID Receptors, Interleukin-4 / therapeutic use* Recombinant Proteins / therapeutic use Spleen / immunology |
| Grant Support | |
ID/Acronym/Agency:
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R01 AI44218-01/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Interleukin-4; 0/Recombinant Proteins; 187348-17-0/Interleukin-12 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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