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

Tatsushi Katakura, Makiko Kobayashi, Kazuhiko Fujita, David N. Herndon, Richard B. Pollard, Fujio Suzuki

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

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 × 103 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.

Original languageEnglish (US)
Pages (from-to)363-370
Number of pages8
JournalClinical Immunology
Volume105
Issue number3
DOIs
StatePublished - Dec 1 2002

Keywords

  • HSV-1
  • IL-12
  • SCID chimera
  • Thermally injured patients
  • sIL-4R

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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