Interleukin‐12 protects thermally injured mice from herpes simplex virus type 1 infection

Severe burn injury is associated with increased susceptibility to severe herpesvirus infections. Type 2 cytokines [interleukin (IL)‐4 and IL‐10] released from burn‐associated CD8+ type 2 T cells (BA‐type 2 T cells) have been shown to play a role in the increased susceptibility of thermally injured mice (TI‐mice) to herpes simplex virus type 1 (HSV‐1) infection. Because IL‐12 has been shown to inhibit the generation of type 2 T cells, murine rIL‐12 was injected into TI‐mice exposed to HSV‐1 to determine whether IL‐12 could influence HSV‐1 infections in individuals bearing type 2 T cells. rIL‐12 improved the resistance of TI‐mice or mice inoculated with T6S cells (a BA‐type 2 T cell clone) against HSV‐1 infection. Type 2 cytokines were detected in sera of TI‐mice or mice inoculated with T6S cells (T6S‐mice). However, treatment of TI‐mice or T6S‐mice with rIL‐12 inhibited type 2 cytokine production in the sera of these mice. All TI‐mice exposed to a lethal dose of HSV‐1 survived when they were treated with a mixture of monoclonal antibodies (mAbs) against type 2 cytokines. Staphylococcal enterotoxin A [an interferon‐γ (IFN‐γ) inducer] stimulated serum IFN‐γ production in TI‐mice and T6S‐mice treated with rIL‐12, whereas no IFN‐γ was produced in mice treated with saline. These results suggest that IL‐12 has the potential to protect TI‐mice infected with a lethal dose of HSV‐1 via a shift to type 1 T cell responses from type 2 T cell responses.

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