Tolerance to the pyrogenic action of intravenously injected virus has been studied in rabbits given either PR8 strain of influenza A virus or Newcastle disease virus (NDV). The following findings suggest that the capacity of the animal to release an endogenous pyrogen is a critical factor. (a) Viruses produce fever by the release of endogenous pyrogen. (b) Tolerance to the pyrogenic effect of r...

The involvement of nitric oxide (NO) in tolerance development to endotoxin has been proposed because peripherally administered NG-nitro-L-arginine methyl ester (L-NAME) (NO synthases inhibitor) delays the endotoxin tolerance formation. Since L-NAME is capable of crossing the blood-brain barrier, the question arises of where activity of NO synthases (inside or outside the blood-brain barrier) is...

1. A relationship between bacterial endotoxin absorbed from the gut and acute renal failure has been postulated. Experiments employing either the endotoxin-tolerant state or the enhancement of endotoxin injury were undertaken to test this relationship in rats. 2. Endotoxin tolerance was induced by the administration of increasing doses of Escherichia coli 026 lipopolysaccharide. The severity of...

Treatment of rats with recombinant human TNF initially causes a marked decrease in food intake, a loss of body weight, and a negative nitrogen balance. These alterations normalize with continued twice daily intraperitoneal injections of the same dose. Rats tolerized to TNF in this manner are refractory to a lethal dose of TNF. Also, TNF-pretreated and -tolerized rats have prolonged survival and...

This laboratory has proposed that endogenous gut-derived bacterial endotoxin primes the pancreatic secretion of insulin in normal rats. Endogenous lipopolysaccharide (LPS) is continually absorbed from the gut into intestinal capillaries, and low-grade portal venous endotoxemia is the status quo. Under physiologic conditions, Kupffer cells of the liver totally phagocytize and degrade endotoxin f...

By SHELDON M. WOLFF, MELVIN RUBENSTEIN, JOHN H. MULHOLLAND AND DAVID W. ALLING T HE PROFOUND HEMATOLOGIC alterations evoked in experimental animals following endotoxin administration have been considered to play a major role in the pathogenesis of some of the biologic effects produced by these lipopolysaccharides. Marked leukopenia, primarily granulocytopenia, and subsequent granulocytosis as w...

Initial exposure of monocytes/macrophages to LPS induces hyporesponsiveness to a second challenge with LPS, a phenomenon termed LPS tolerance. Molecular mechanisms responsible for endotoxin tolerance are not well defined. We and others have shown that IL-1R-associated kinase (IRAK)-M and SHIP-1 proteins, negative regulators of TLR4 signaling, increase in tolerized cells. TGF-beta1, an anti-infl...

By SHELDON M. WOLFF, MELVIN RUBENSTEIN, JOHN H. MULHOLLAND AND DAVID W. ALLING T HE PROFOUND HEMATOLOGIC alterations evoked in experimental animals following endotoxin administration have been considered to play a major role in the pathogenesis of some of the biologic effects produced by these lipopolysaccharides. Marked leukopenia, primarily granulocytopenia, and subsequent granulocytosis as w...

The effect of repeated stimulation on both the interferon and antibody systems and on reticuloendothelial activity was studied by injection of endotoxin 2 days before injection of (poly rI):(poly rC). A single injection of endotoxin or (poly rI):(poly rC) increased or decreased the response in each system depending on the time of administration. If the injection of (poly rI):(poly rC) was prece...