Abstract

It is well demonstrated that serial endotoxin injections produce endotoxin tolerance and elevate natural resistance. However, such injections may also have harmful effects such as high fever, hypotension and abortion. For this reason LPS injections are not suitable to enhance nonspecific resistance in endotoxin-sensitive mammalian species including man. Various techniques have been designed (physical, chemical, etc.) for the detoxification of endotoxins while the beneficial effects were maintained. Perhaps one of the best detoxification techniques is treatment with ionizing radiation. The irradiation of LPS with 60Co (100-200 kGy) decreased its toxicity in a dose-dependent manner. Such radiodetoxified endotoxin (RD-LPS) preparations showed decreased toxicity whereas the beneficial effects were preserved (150 kGy: TOLERIN®). These findings have been confirmed in other laboratories. Irradiation causes marked chemical alteration in LPS, such as the decrease of glucosamine, KDO and fatty acids. A single parenteral injection of TOLERIN® is capable of preventing the various forms of shock in experimental animals. This preparation has a membrane-stabilizing effect and thereby can prevent the membrane-damaging effect of LPS and of some cytostatic agents. Unlike endotoxin, TOLERIN has barely any hypotensive effect and pretreatment with this preparation can prevent practically all the haemodynamic changes induced by LPS. LPS plays an important role in the pathogenesis of the intestinal syndrome of radiation disease, which may be prevented by up to 70% in rats with RD-LPS pretreatment. TOLERIN retains the adjuvant activity of LPS and it is a good adjuvant for inactivated virus vaccines. TOLERIN can also evoke the regeneration of the immune system in irradiated animals. The decrease of nonspecific resistance in immunodeficient or immunosup-pressed patients is the most important cause of opportunistic infections that may lead to sepsis, endotoxaemia, pneumonia and so on. Organ transplant recipients commonly die of septicaemia. Antilymphocyte serum (ALS) is used in such patients as an immunosuppressant. The augmentation of natural resistance and the induction of endotoxin tolerance are of major significance in such patients. We found that in ALS-treated rats RD-LPS induced tolerance against the lethal dose of LPS. This experiment demonstrated that in spite of the suppressive effect of ALS on T lymphocytes the induction of LPS tolerance (the enhancement of natural resistance) was normal. Facultative pathogenic organisms may flourish and cause disease when specific and nonspecific resistance is impaired. RD-LPS could produce significant proliferation of lymphoid cells in germ-free animals which are immunodeficient. Many other beneficial effects are preserved by RD-LPS preparations, such as the activation of macrophages and of the reticuloendothelial system, antitumour activity, etc. On the basis of these favourable experimental results, TOL-ERIN was tested on 350 surgical patients suffering from gastrointestinal tumours, on other patients suffering from AIDS and on cancer patients treated with CYSPLATINC. TOLERIN treatment prevented sepsis and activated bone marrow function in these patients.

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Natural Treatments For Psoriasis

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