Therapeutic effects of IL-12 combined with benzoylmesaconine, a non-toxic aconitine-hydrolysate, against herpes simplex virus type 1 infection in mice following thermal injury

Makiko Kobayashi, Hitoshi Takahashi, David N. Herndon, Richard B. Pollard, Fujio Suzuki

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

IL-12 is an inducer of type 1 T cell responses, which are essential in host defense against herpes simplex virus type 1 (HSV-1) infection. However, type 1 T cell responses are not elicited by IL-12 in thermally injured mice (TI-mice) that routinely have a predominance of burn-associated type 2 T cell responses. In our previous studies, benzoylmesaconine (BEN, an aconitine derivative extracted from heated-Aconiti tuber) induced the generation of CD4+ T cells antagonistic to type 2 T cells (BEN-CD4+ T cells). In the present study, the effects of a combination therapy using IL-12 and BEN to treat severe HSV-1 infection in TI-mice were investigated. When TI-mice were treated with either IL-12 (500U per mouse) or BEN (1μg/kg) alone, they did not resist HSV-1 infection. However, 60-80% of TI-mice exposed to HSV-1 survived after they received IL-12 and BEN or BEN-CD4+ T cells in combination. After stimulation with anti-CD3 mAb in vitro, IFN-γ was not produced in cultures of splenic T cells from TI-mice exposed to HSV-1 and treated with either IL-12, BEN or BEN-CD4+ T cell alone. However, IFN-γ production was induced by the mAb stimulation in the cultures of T cells from infected mice treated with IL-12 and BEN or BEN-CD4+ T cells in combination. These results suggest that the combination therapy of IL-12 (an inducer of type 1 T cell responses) and BEN (an inhibitor of type 2 T cell responses) may protect TI-mice from severe HSV-1 infection.

Original languageEnglish (US)
Pages (from-to)37-42
Number of pages6
JournalBurns
Volume29
Issue number1
DOIs
StatePublished - Feb 1 2003

Keywords

  • Benzoylmesaconine
  • Burn injury
  • Herpes simplex virus
  • IL-12

ASJC Scopus subject areas

  • Surgery
  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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