Endotoxin tolerance in rats: Expression of TNF-alpha, IL-6, IL-10, VCAM-1 and HSP 70 in lung and liver during endotoxin shock

Endotoxin can induce a state of tolerance against its own pathological effe cts, commonly referred to as endotoxin tolerance. This phenomenon has been found to be associated with reduced serum levels of cytokines such as TNF-a lpha, TL-I, IL-6 and IL;-10. In the present study the expression of TNF-alp ha, IL-6, IL-10, the adhesion molecule VCAM-1 and the heat shock protein 70 was determined in vivo in lung and liver of LPS;tolerant and naive rats by means of semiquantitative RT-PCR after i.v. LPS injection; TNF alpha, IL-6 , IL-10, HSP 70 and VCAM-1 were induced in lung and liver after LPS injecti on. In liver and lung of endotoxin-tolerant rats TNF-alpha and IL-6 mere in duced to a lower degree after LPS treatment when compared to non-tolerant c ontrols, The LPS-induced IL-10 expression was also slightly attenuated in t he lung of tolerant rats, but in the liver no differences between tolerant and non-tolerant animals were observed. HSP 70 and VCAM-1 were expressed af ter systemic LPS treatment in liver and lung. The degree of induction, howe ver, was the same in tolerant and untreated controls. The presented data sh ow that endotoxin tolerance is reflected by a reduced cytokine expression i n lung and liver in vivo. On the other hand, levels of expression of the ad hesion molecule VCAM-1 and the stress protein HSP 70 do not appear to be ch anged by endotoxin tolerance. In 1999 Academic Press.