Radio-detoxified endotoxin activates natural immunity: a review.

Abstract

It is well demonstrated that serial endotoxin injections produce endotoxin tolerance and elevate the natural immunity/resistance. However, such injections may also have harmful effects such as high fever, hypotension and abortion. For this reason endotoxin (LPS) injections are not suitable to enhance nonspecific resistance in endotoxin-sensitive species like man. Various techniques have been designed (physical, chemical, etc.) for the detoxification of endotoxins while the beneficial effects are maintained. Perhaps one of the best detoxification techniques is the treatment with ionizing radiation. The irradiation of LPS with 60Co (150 kGy) decreased its toxicity in a dose-dependent manner. Such radio-detoxified endotoxin (RD-LPS) preparations show decreased toxicity whereas the beneficial effects were preserved. Irradiation causes marked chemical alterations in LPS, such as a decrease of glucosamine, ketodeoxyoctonic and fatty acids. A single parenteral RD-LPS injection prevents various forms of shock in experimental animals. This preparation has a membrane-stabilizing effect, and thereby it can prevent the membrane-damaging effect of LPS and of some cytostatic agents. Unlike endotoxin, RD-LPS has little hypotensive effects, and the pretreatment with this preparation can prevent practically all the hemodynamic changes induced by LPS. LPS plays an important role in the pathogenesis of intestinal syndrome of radiation disease, which may be prevented by RD-LPS pretreatment up to 70% in rats. RD-LPS retains the adjuvant activity of LPS, and it serves as a good adjuvant for inactivated virus vaccines. RD-LPS can also evoke the regeneration of the immune system in irradiated animals. The decrease of nonspecific resistance in immunodeficient or immunosuppressed patients is the most important cause of opportunistic infections that may lead to sepsis like in endotoxaemia and pneumonia. 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. In ALS-treated rats RD-LPS induces also tolerance against the lethal dose of LPS. This demonstrates that in spite of the suppressive effect of ALS on T-lymphocytes the induction of LPS tolerance (the enhancement of natural resistance) remains normal. Facultative pathogenic organisms may flourish and cause disease when specific and nonspecific resistance is impaired. RD-LPS can produce a 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 and antitumor activity. On the basis of these favorable experimental results, RD-LPS has been tested on 350 surgical patients suffering from gastrointestinal tumors, patients suffering from acquired immunodeficiency syndrome (AIDS) and cancer patients treated with CYSPLATIN. RD-LPS treatment prevented sepsis and activated the bone marrow function in these patients.