Review of the molecular requirements of endotoxic actions

Old and new data are compiled to confirm earlier claims and to substantiate new concepts regarding the structural requirements of endotoxic reactions. The major points can be summarized as follows. (1) Recent results obtained by the use of synthetic analogues of lipid A structures proved unequivocally that the lipid moiety of the endotoxin is the carrier of toxic properties. Incomplete or attenuated structures are inactive in some or all toxic reactions, depending on the extent of deviations from the structure of the native product. (2) On the other hand, some beneficial reactions can be initiated not only by the complete structures but by their structural remains, which are no longer toxic. (3) Some of the split products in the lipid-free and polysaccharide-rich preparations can induce beneficial reactions. (4) Gram-negative bacteria can produce endotoxin-unrelated and beneficial compounds. Conventional endotoxin preparations are heterogeneous and often contain some of these unrelated substances. (5) Elucidation of the exact structural requirements of endotoxic reactions has just begun. It appears to be safe to predict that individual reactions will require highly specific structures or physicochemical properties. The potential rewards of such research might be quite significant by facilitating our understanding of the molecular events of the beneficial effects of endotoxins and by directing the search for preparations with therapeutic applications.