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.
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 (500 U per mouse) or BEN (1 microg/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- 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- 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.
Kobayashi
Makiko
M
Department of Internal Medicine, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0435, USA.
Takahashi
Hitoshi
H
Herndon
David N
DN
Pollard
Richard B
RB
Suzuki
Fujio
F
D000157:Aconitine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D002056:Burns / Q000150:complications* / Q000276:immunology / Q000821:virology; D006566:Herpesviridae Infections / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000627:therapeutic use*; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; C085283:benzoylmesaconine; D000157:Aconitine