Effect of a combination therapy between IL-12 and soluble IL-4 receptor (sIL-4R) on Candida albicans and herpes simplex virus type I infections in thermally injured mice.
The effectiveness of a combination using IL-12 and soluble IL-4 receptor (sIL-4R) to treat severe infections of herpes simplex virus type 1 (HSV-1) and Candida albicans in thermally injured mice was investigated. Although sIL-4R decreased burn-associated type 2 T-cell responses, the effect of sIL-4R was minimal on the morbidity and mortality of thermally injured mice exposed to 250 times LD50 of HSV-1 or 10 times LD50 of C. albicans. Compared with 100% mortality in control mice, mortality for HSV-1 and C. albicans was 40 and 20%, respectively, in thermally injured mice that received IL-12 and sIL-4R in combination. After stimulation with anti-CD3 monoclonal antibody, splenic T cells from thermally injured mice exposed to large amounts of HSV-1 or C. albicans did not produce gamma interferon (IFN-gamma) into their culture fluids. However, IFN-gamma was produced by splenic T cells from thermally injured and infected mice treated with IL-12 and sIL-4R in combination. These results suggest that therapeutic treatment with a combination of IL-12 and sIL-4R may be effective by inducing type 1 T-cell responses in thermally injured mice exposed to large amounts of HSV-1 or C. albicans.
Kobayashi
Makiko
M
Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 77555, USA.
Takahashi
Hitoshi
H
Herndon
David N
DN
Pollard
Richard B
RB
Suzuki
Fujio
F
D000818:Animals; D002056:Burns / Q000150:complications* / Q000276:immunology / Q000382:microbiology; D002176:Candida albicans / Q000187:drug effects / Q000276:immunology; D002177:Candidiasis / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D006561:Herpes Simplex / Q000188:drug therapy* / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018664:Interleukin-12 / Q000627:therapeutic use*; D015847:Interleukin-4 / Q000097:blood; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D019948:Receptors, Interleukin-4 / Q000627:therapeutic use*; D013154:Spleen; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
D019948:Receptors, Interleukin-4; D018664:Interleukin-12; D015847:Interleukin-4