germanium and Burns

Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), is a major cause of sepsis in patients who are immunosuppressed by their burns. In this study, an immunological regulation of MRSA infection was attempted in a mouse model of thermal injury. SCIDbg mice were resistant to MRSA infection, while SCIDbgMN mice (SCIDbg mice depleted of neutrophils and macrophages (Mphi)) were susceptible to the same infection. Also, thermally injured SCIDbg mice were shown to be susceptible to MRSA infection. On the other hand, the resistance of SCIDbgMN mice to the infection was completely recovered after an inoculation with Mphi from normal mice. However, anti-MRSA resistance was not shown in SCIDbgMN mice inoculated with Mphi from thermally injured mice. Mphi from MRSA-infected thermally injured mice were identified as alternatively activated Mphi, and Mphi from MRSA-infected unburned mice were characterized as classically activated Mphi. Mphi from thermally injured SCIDbg mice previously treated with 2-carboxyethylgermanium sesquioxide (Ge-132) protected SCIDbgMN mice against MRSA infection. Ge-132 has been described as an inhibitor of alternatively activated Mphi generation. These results suggest that MRSA infection in thermally injured patients is controlled immunologically through the induction of anti-MRSA effector cells and elimination of burn-associated alternatively activated Mphi, which are cells that inhibit the generation of classically activated Mphi.

Topics: Animals; Burns; Cells, Cultured; Chemokines; Cytokines; Disease Models, Animal; Disease Susceptibility; Germanium; Immunity, Innate; Interferon Inducers; Macrophages; Methicillin Resistance; Mice; Mice, SCID; Neutrophils; Organometallic Compounds; Propionates; Staphylococcal Infections; Staphylococcus aureus; Wound Infection

As reported previously, gamma interferon (IFN-gamma) production was selectively decreased in thermally injured mice (TI-Mice) and spleen cell cultures from the mice following stimulation with various IFN inducers. The decrease in IFN production was associated with splenic suppressor macrophages. The present study demonstrated that TI-Mice treated with Ge-132 (TGe-Mice) produced IFN following stimulation with IFN-gamma inducers. The level of IFN activity detected in the sera of TGe-Mice approximated that of controls. Similar results were obtained when spleen cells prepared from TGe-Mice were stimulated with IFN-gamma inducers in vitro. While transfer of spleen cells from TI-Mice resulted in the suppression of IFN production in normal mice (N-Mice) stimulated with IFN-gamma inducers, the transfer of spleen cells derived from TGe-Mice did not induce suppression of IFN production in N-Mice. Mononuclear cells (MNC) prepared from N-Mice produced IFN following concanavalin A (Con A) stimulation when they were co-cultured with macrophage-enriched populations (PAC) obtained from the spleens of TGe-Mice. In contrast, MNC stimulated with Con A did not produce IFN activity when they were co-cultured with PAC of TI-Mice. These results suggest that the generation of suppressor macrophages in TI-Mice may be altered by the administration of Ge-132.

Topics: Animals; Antineoplastic Agents; Burns; Concanavalin A; Enterotoxins; Female; Germanium; Interferon Inducers; Interferon-gamma; Kinetics; Macrophages; Mice; Mice, Inbred BALB C; Newcastle disease virus; Organometallic Compounds; Poly I-C; Propionates

Topics: Burns; Burns, Chemical; Dermatitis; Dermatitis, Contact; Eye Burns; Germanium; Guinea Pigs; Mice; Rabbits; Research; Toxicology