Bacterial endotoxins have been studied for more than 200 years, and the earliest relevant research began with the observation of decaying animals.
In the 18th century, Albrecht von Haller (1708-1777) injected putrid liquid extracted from rotting fish or meat into animals intravenously and found that it could cause fever and other disease symptoms in animals, while extracts of fresh fish or meat did not cause febrile reactions. At that time, it was thought that food produced toxic substances that could cause heat and disease during the process of degradation and decay.
As early as the 19th century, attempts were made to identify this decaying toxin, which Ernst von Bergmann (1836-1906) named sepsin. It should be said, Dane Peter LPanum was the first scientist to systematically and scientifically study this toxin. In 1874, he published ** clearly stating that this decaying toxin is not volatile, is not a simple end product of decaying or fermenting tissues, and is not a living microorganism, this toxin may ** microorganisms;The toxin is heat-resistant and is not an enzyme;Soluble in water, insoluble in pure ethanol;The protein-like substances in the decaying fluid are not toxic in themselves, but they can absorb toxins to the surface, and the toxic components are at least partially eluted from the sediment;An injection of 12 mg of concentrate is enough to cause a high fever that can cause death in the dog. Based on what we now know about endotoxins, in fact, the results of Panum's research have already involved endotoxins. Therefore, it can be said that he was the first researcher to describe the properties of endotoxins.
Because the main manifestation of this toxin is to cause fever, in the 19th century, most people called it pyrogenic material or pyrogen.
The term "thermogenic substance" was first proposed by Theodor Billroth (a professor of surgery), who described it in his 1862 book, "Thermogenic substances" are found not only in decaying fluids and fresh pus, but also in dry decaying matter and dried pus. Sir John Burdon-Sanderson (1828-1905, British physiologist and pathologist) further referred to "thermogenic substances" as "pyrogens" in 1896, and on the basis of the research of Panum and von Beugmann, Burdon-Sanderson obtained at least partially purified pyrogens, proposing for the first time the ** of thermogenic substances Problem: Endogenous (pyrogens present in blood or tissue fluids) and exogenous (from microorganisms).
It was only in the late 19th and early 20th centuries that it became clear that infections were caused by microorganisms. Previously, endemic or endemic diseases such as plague and cholera were thought to be caused by miasma, an invisible volatile substance in or under the soil, which was called "badair", which is the origin of the word "malaria". Therefore, it was believed at the time that the spread of this infection was not from person to person, but through environmental factors, such as poison gas. On the other hand, doctors clearly observe that some diseases, such as syphilis, are transmitted from person to person, rather than through bad air. Therefore, it was early thought that there were two ways in which infection occurred: poison gas and contagion.
Louis Pasteur (1822 1895) was the first to unequivocally confirm that infectious diseases are caused by microorganisms. He believes that these microorganisms exist in airborne dust and can travel everywhere, invade wounds, and multiply in wounds, causing infections. Although Billroth believed that the infection was caused by bacteria, he believed that the bacteria themselves exist in the healthy tissues of the host, and when stimulated by inflammation, the bacteria are activated and multiplied, that is, the "endogenous spoilage theory". German bacteriologist Edwin Klebs (after whom the intestinal bacterium Klebsiella is named) believes that the bacteria that cause infections are external, bacteria can invade healthy and stimulated tissues, and produce thermogenic substances during the occurrence of infection. In 1884, the Danish physician Hans-Christian Gram (1853-1939) invented a dyeing technique that is still widely used today, the gramstain method. This method can be used to divide all bacteria into two groups: gram-positive bacteria and gram-negative bacteria.
As it became clear that infections were caused by microorganisms, the study of pyrogens** was also transferred from decaying tissues to microorganisms. Gust**e Roussy (1874-1948) isolated two substances from bacteria for the first time: one that caused low-grade fever called frigorigenineThe other causes high fever and is called pyretogenine. He believed that these substances were located inside the bacteria and were released after being dissolved by enzymes. Ludwig Brieger then discovered that typhoid bacilli can also produce a toxic substance, typhoxin toxin. The term "toxin" was first coined by Brieger. Subsequently, a high-molecular-weight protein-like toxic substance, known as toxalbumin, was isolated from cultures of other bacilli as a sterile white powder. Further research has found that many pathogenic bacteria produce toxic substances that can cause lethal reactions. Because the toxins isolated at that time all exhibited protein-like properties, all bacterial toxins were once thought to be proteins.
*: "Basic and Clinical Basis of Bacterial Endotoxin", Author: Jiang Jianxin, if there is any infringement, please contact to delete, thank you!