Stimulation of Nonspecific Resistance by Radio-Detoxified Endotoxin

Abstract

Different immunodeficiency states and infections in immunosuppressed patients are serious problems of medicine. Specific humoral and cellular immune responses are widely investigated, but mechanisms of nonspecific resistance (NSR) gained attention just recently (8). Serious decrease of NSR might be the cause of opportunistic infections in patients receiving radiation therapy, cytotoxic or immunosuppressive drugs, or suffering from certain viral diseases, e.g., AIDS (1–5). Recently some immunomodulators are tested as potential stimulators of NSR. Among them the bacterial endotoxin (LPS) is one of the most active materials. Unfortunately, the parenteral administration of LPS is associated with untolerable side effects, so this compound (in its original form) is not suitable for enhancing of NSR in endotoxinsensitive mammals or in humans. Various attempts have been made to modify LPS to reduce its toxicity without altering its beneficial immunological activities (15, 17, 18). Perhaps, one of the best detoxification techniques is the use of ionizing radiation (1, 3, 5, 13, 16). As it was demonstrated by many in vitro and in vivo studies irradiation of LPS with ⁶⁰Co-gamma (150 kGy) decreased its harmful side effects in a dose dependent manner (1–6, 10, 13, 19), but this radiodetoxified LPS preparation (RD-LPS or so-called TOLERIN) preserved the beneficial effects of LPS (1–3, 5, 13). These findings are confirmed by other authors, too (9, 14). Irradiation modifies markedly the chemical structure of LPS, decreases the amount of certain constituents: e.g., glucosamine, KDO, fatty acids, etc. (9, 11, 12).