Pathogenesis of atoxinogenic strains of gram--negative bacteria--a hypothesis.

Textbooks of medical microbiology attribute to endotoxin a primary pathogenic role in diseases caused by nontoxinogenic gram negative bacteria. There is little experimental data to support this claim while some observations indicate the contrary. The possibility cannot be ignored that our understanding of the biological effects of endotoxin is based on the administration of endotoxin as a bolus rather than as a continuous release in small amounts over a period of hours or days as probably occurs during an infection. Results are described that clearly show how different the response can be under the two conditions. It is suggested, moreover, that mediators formed primarily by macrophages stimulated by endotoxin may contribute significantly to the pathogenesis of these diseases.