RESUMEN
A decline in the immunopotential of the host plays an essential role in the occurrence of infections with methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) or other multi-drug resistant microorganisms. In the present study, mytomycin C (MMC)-treated mice with or without the infection of MRSA were used to examine the bacteriostatic action as well as the immunopotentiating action of the promising herbal medicine, Hochu-ekki-to (HET). Basic experimental data showed the drug to be effective in the treatment of MRSA infection. Eight to ten week old male C57BL mice were injected with MMC at a dosage of 5mg/kg/day to inhibit the bone marrow, thus creating a mouse model with reduced immunopotential. A powder extract of HET was administered orally at a dosage of 500mg/kg/day for seven consecutive days. For the infection of MRSA 1×10<sup>9</sup> cell were injected intraperitoneally. Peritoneal macrophages were prepared by the adherence technique. Macrophage migration, phagocytic activity, and the bactericidal activity were examined by the Boyden chamber method, by the phagocytosis for fluorescent-activated latex beads, and by the nitroblue tetra zolium (NBT) reduction test, respectively.<br>After the administration of HET, the number of white blood cells in the MMC-treated mice recovered to 80% of the normal value. In addition, the phagocytic activity of macrophages increased to 50%, although that of the non-treated group was only 20%. The bactericidal activity also recovered to a level close to the normal value. The ratio of neutrophils in the HET administered MMC-treated group increased to 2.2% (normal mice, 2.6%) whereas that of the MMC-treated control group was 0.5%. Concerning the function of the immunological cells, IL-1beta and IFNgamma levels were recovered by treatment with HET, as observed by IL-1beta, IL-2 and IFNgamma monitoring. The bacterial count in the liver of the MRSA challenged mice, with or without HET administration peaked 6 hours after the challenge. The number of the group with HET administration was, however, much greater than that of the group without HET administration. The bacteria count in the blood showed an increase 12 and 24 hours after the challenge. Even 24 hours after the challenge, a significant number of bacterial cells existed in the blood of the group without HET administration, whereas only a small number of cells were detected 6 hours after the challenge. All of the control mice died 8 days after the MRSA challenge, whereas the survival rates were 60% for HET treatment, 40% for the vancomycin treatment, and 80% for the HET plus vancomycin treatment, respectively.<br>As we move towards a society with a high percentage of elderly people, the authors believe Chinese herbal medicine, which activates the immunopotential, will be very helpful in the treatment of opportunistic infections that are common among elderly patients.
RESUMEN
Resistance to facultative intracellular bacterial pathogens depends on acquired cell-mediated immunity and activation of macrophages by T- lymphocytes. Gamma interferon (IFN-gamma) is believed to be an important mediator of acquired cell-mediated immunity. In the present study, we evaluated the effect of Hochu-ekki-to (HET) on the survival rate and cytokine production with <i>Salmonella</i> infection model by using EL-4-bearing C57BL/6 mice. 1) When HET was administered orally to the tumor-bearing mice, it extended the survival time compared with non-treated controls in experimental infection by virulent strain 116-54. 2) The effect of HET on production of IFN-gamma in cultured splenocytes was tested by using the tumorbearing mice immunized with attenuated live SER strain. Spleen cells prepared from the mice treated with HET produced high levels of IFN-gamma compared with non-treated controls.<br>The results indicated that orally administered-HET enhanced protective ability to primary <i>Salmonella</i> infection and production of IFN-gamma accompanied by vaccination in EL-4-bearing C57BL/6 mice.