Auswirkung von O3/O2-Gasgemisch im Peritoneum auf Zytokinproduktion und Schmerzinduktion

Ozone (O3) is a metastable gas, which disaggregates with the formation of reactive oxygen combinations. Due to its powerful oxidation ability and antiseptic qualities, it is often used in human medicine as an additional therapeutic agent externally. Little is currently known about the pain and immunomodulational effects of intraperitoneally applied O3. One aim of this study was the investigation of the pain aspect of intraperitoneal insufflation of a O3/O2-gas mixture. A further aim was the collection of evidence of ozone-effects on the immune system. For the detection and characterization of a possible burden of pain among intraperitoneal O3/O2-insufflation-therapy we initially performed a writhing response test. The behavior of C-57BL/6-mice, following intraperitoneal insufflation of a O3/O2-gas mixture, was compared with that of mice following intraperitoneal administration of pure oxygen (100% pure O2), acetic acid (7% H3C-COOH, positive control) or 0.9% NaCl solution (Sham). After the writhing test, the mice were decapitated and tissue samples were taken (including spinal cord and spleen). As a second step, an analysis was made of a possible pain component of O3/O2-pneumoperitoneum whereby the c-fos-gene-expression in the thoracolumbar spinal cord was mesured, using real-time PCR (qPCR). Furthermore, the effects of ozone on the immune system were investigated. For this purpose, the change of gene expression of the proinflammatory cytokines IL-6 and IL-1ß in the secondary lymphatic mouse spleen tissue was determined by performing another qPCR. The result of the writhing behavior experiment precludes the occurrence of visceral pain during intraperitoneal O3/O2-insufflation. By insufflation of inert O2-gas there was no sign of writhing responses, therefore stretching artifacts could be excluded. Measurement of significantly increased c-fos-gene-expression in the spinal cord suggested a perception of pain after O3/O2-insufflation, despite reduced writhing actions during the writhing behavior experiment. From qPCR-data it is concluded that neither the H3C-COOHintraperitoneal- injection nor the insufflation of O3/O2-gas-mixture provide immunostimulative effects. This means that a therapeutic application of O3/O2 gas mixture should only be performed under adequate analgesia. A pathological immune stimulation caused by intraperitoneal O3/O2 insufflation however, is not to be expected.