내독소 내성(Endotoxin Tolerance)에 관한 실험적 연구 = An Experimental Study on Endotoxin Tolerance in Dogs

다국어 초록 (Multilingual Abstract)

Endotoxin is a lipo-polysaccharide protein complex derived from gram-negative bacteria, which can be introduced into the blood stream of the human body in various circumstances and causes so-called "endotoxin shock". Septicemia caused by gram=negative bacteria has been recognized at least since 'the report of Jacob(1909) and Felty aril Keefer(1924). However, septic shock was first described as a clinical entity by Waisbren(1951), and in subsequent years many experimental studies were conducted using endotoxin in dogs.
Endotoxin, given in appropriate doses to the dog, produces hypotension, rise in portal pressure with simultaneous constriction of hepatic veins, great increase in the weight of the liver, and mesenteric ischemia (Sabiston, 1972). Recently, it has been' generally considered that any irreversibility of shock is a result from the insult of endotoxin (Smiddy and Fine, 1957; Fine et al., 1960; Siegel et al., 1967).
Beeson(1947) suggested possible tolerance to the pyrogenic effect of endotoxin, and Atkins and Wood(1955) observed that tolerant animals cleared endotoxin, which was administered intravenously, more rapidly from the blood stream, and numerous experimental studies have been made on endotoxin shock (Dubos and Schaedler, 1956; Schweinburg et al., 1959; Smith et al., 1957; Carey et al., 1958; Freedman, 1960; Greisman et al., 1963; Rutenburg et al., 1967; Filkins and Di Luzio, 1968; Haugen, 1972; Trejo and Di Luzio, 1971).
Endotoxin tolerance is the state of enhanced resistance of animals against thetoxic effects of bacterial endotoxins, and the tolerance state is usually induced by the prior administration of multiple sublethal doses of endotoxin (Beeson,1947; Carey et al., 1958; Freedman, 1960; Greisman et al., 1963; Tsagaris et al., 1969; Trejo and Di Luzio, 1972).
Although the mechanism of endotoxin tolerance is still in controversy, it is generally thought that the endotoxin tolerance state is intimately related to phagocytic activity of the reticuloendothelial system (Good and Thomas, 1952; Schweinburg and Fine, 1955; Schweinburg et al., 1955; Zweifach et al., 1957; Fine et aI., 1958; Carey et al., 1958; Greisman et al., 1963; Arredondo and Kampschmidt, 1963; Filkins and Di Luzio, 1968), and, furthermore, related to the phagocytic activity of macrophages of the liver and spleen(Collins and Wood, 1959; Rutenburg et al., 1960; Cohn and Wiener, 1963; Cline et al., 1968; Filkins, 1971; Fine, 1972).
Tsagaris et al. (1969) demonstrated in the hemodynamic study of endotoxin shock that tolerant animals were less susceptible than the nontolerant to hemodynamic changes such as blood pressure and cardiac output,and blood pressure and cardiac output were restored more rapidly in the tolerant animals than in the nontolerant.
In mice pretreated with various agents, such as BCG and diethylstilbesterol to activate the reticuloendothelial function, increased susceptibility to endotoxin challenge was observed, and it was suggested that endotoxin tolerance is not related to the activation of reticuloendothelial function(Suter et al.,1958;Benacerraf et al., 1959; Stuart and Cooper, 1962). Moreover, tolerance to pyrogenicity of endotoxin was observed in the presence of normal phagocytic activity of the reticuloendothelial system, and activation of the reticuloendothelial system was not necessarily required in the development of endotoxin tolerance (Greistn,n et al., 1963).
It is well known that liver and spleen consist of major reticuloendothelial tissue but it is not yet clear which organ participates more actively to detoxify endotoxin in the blood stream. It has been also suggested that distribution of endotoxin in the body is different between the tolerant and the nontolerant animals(Smith et al., 1957; Carey et al., 1958; Rutenburg et al., 1965; Alper et al., 1967).
In order to provide additional information on endotoxin tolerance, a comparative study was conducted on the hemodynamic changes, antibody formation, endotoxin uptake, and histopathologic alterations in the reticuloendothelial system of endotoxin tolerant and nontolerant dogs.