The regulation of burn-associated infections with herpes simplex virus type 1 or Candida albicans by a non-toxic aconitine-hydrolysate, benzoylmesaconine. Part 2: Mechanism of the antiviral action

Immunol Cell Biol. 1998 Jun;76(3):209-16. doi: 10.1046/j.1440-1711.1998.00736.x.

Abstract

In the accompanying paper, the resistance to infections with HSV type 1 (HSV-1) and Candida albicans was improved in thermally injured mice treated with benzoylmesaconine (BEN), an aconitine-hydrolysate isolated from heated Aconiti tuber, or inoculated with splenic CD4+ T cells from BEN-treated mice (BEN T cells). In this paper, therefore, the antiviral mechanism of BEN T cells (or BEN) on the improved resistance of burned mice to the HSV-1 infection was studied. Burn-associated CD + CD11b+ TCRgamma/delta+ type-2 T cells have been shown to be a key on the increased susceptibility of thermally injured mice to infection with HSV-1 or C. albicans. The susceptibility of T6S-mice, mice inoculated with 1 x 10(6) cells/mouse of T6S cells (a clone of burn-associated type-2 T cells), to HSV-1 infection was similar to that of thermally injured mice. The adoptive transfer of BEN T cells to T6S-mice restores their impaired resistance to HSV-1 infection. The type-2 cytokine levels in sera of T6S-mice were decreased after inoculation of BEN T cells. BEN T cells inhibited the type-2 cytokine production by T6S cells when they were cocultured in vitro. BEN T cells, characterized as CD4+ CD28+ TCRalpha/beta+ Vicia villosa (VV) lectin-adherent T cells, showed non-specific ability to inhibit the cytokine production by various type-2 T cells. From the results of the cytokine-producing profile, BEN T cells were shown to be a different subset of CD4+ T cells from Th1 and Th2 cells, although these three CD4+ T cells had similar properties phenotypically. BEN T cells were induced in normal mice 1-4 days after the oral treatment of BEN (1 microg/kg or more). These results suggest that, through the induction of antagonistic CD4+ T cells against burn-associated type-2 T cells, BEN may improve the resistance of T6S-mice (or thermally injured mice) to the infection of HSV-1.

MeSH terms

  • Aconitine / analogs & derivatives*
  • Aconitine / therapeutic use
  • Animals
  • Burns / complications
  • Burns / microbiology*
  • Burns / virology*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Candida albicans / drug effects*
  • Candida albicans / growth & development
  • Candidiasis / etiology
  • Candidiasis / prevention & control*
  • Clone Cells / drug effects
  • Clone Cells / virology
  • Cytokines / biosynthesis
  • Disease Susceptibility
  • Herpes Simplex / etiology
  • Herpes Simplex / prevention & control*
  • Herpesvirus 1, Human / drug effects*
  • Herpesvirus 1, Human / growth & development
  • Hydrolysis
  • Immunophenotyping
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred BALB C
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism

Substances

  • Cytokines
  • benzoylmesaconine
  • Aconitine