Biomaterial Database

Endotoxin tolerance: effects on lethality and macrophage thromboxane (B2) and interleukin 6 production. 1994

H Chen, and P V Halushka, and J A Cook

Department of Physiology, Medical University of South Carolina, Charleston 29425, USA.

The effects of endotoxin pretreatment on induction of in vivo tolerance to endotoxin lethality, and on in vitro stimulated peritoneal macrophage mediators, thromboxane (TX)B2 and interleukin 6 (IL-6) were investigated. Rats were given i.p. injections of S. enteritidis endotoxin on days 1 (100 micrograms/kg) and 2 (500 micrograms/kg), respectively. After 5 days, or after 2-8 weeks of initial pretreatment, either endotoxin-induced mortality was assessed, or peritoneal cells were harvested for the in vitro studies. Endotoxin tolerant rats were resistant (p < .05) to endotoxin lethality for 2 weeks after initial induction of tolerance. In vitro studies with peritoneal macrophages demonstrated that endotoxin or monophosphoryl lipid A stimulated (p < .05) TXB2 production. However, peritoneal cells harvested from endotoxin tolerant rats exhibited suppressed (*p < .05) TXB2 production to both stimuli which persisted for at least 8 weeks. Endotoxin stimulated (p < .05) in vitro levels of IL-6 in control cells, but in contrast to the suppressed TXB2 production in tolerance, also stimulated (p < .05) in vitro IL-6 in the endotoxin tolerant group. Paradoxically, lipid A did not induce IL-6 production in either group. These composite observations suggest that during endotoxin tolerance neither in vitro peritoneal macrophage TXB2 nor IL-6 synthesis temporally correlate with in vivo resistance to lethality.

UI	MeSH Term	Description	Entries
D008070	Lipopolysaccharides	Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)	Lipopolysaccharide,Lipoglycans
D008264	Macrophages	The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)	Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008297	Male		Males
D010537	Peritoneum	A membrane of squamous EPITHELIAL CELLS, the mesothelial cells, covered by apical MICROVILLI that allow rapid absorption of fluid and particles in the PERITONEAL CAVITY. The peritoneum is divided into parietal and visceral components. The parietal peritoneum covers the inside of the ABDOMINAL WALL. The visceral peritoneum covers the intraperitoneal organs. The double-layered peritoneum forms the MESENTERY that suspends these organs from the abdominal wall.	Parietal Peritoneum,Peritoneum, Parietal,Peritoneum, Visceral,Visceral Peritoneum,Parametrium,Parametriums
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004361	Drug Tolerance	Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL.	Drug Tolerances,Tolerance, Drug,Tolerances, Drug
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012481	Salmonella Infections, Animal	Infections in animals with bacteria of the genus SALMONELLA.	Animal Salmonella Infection,Animal Salmonella Infections,Infection, Animal Salmonella,Infections, Animal Salmonella,Salmonella Infection, Animal
D012772	Shock, Septic	Sepsis associated with HYPOTENSION or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include but are not limited to LACTIC ACIDOSIS; OLIGURIA; or acute alteration in mental status.	Endotoxin Shock,Septic Shock,Shock, Endotoxic,Shock, Toxic,Toxic Shock,Toxic Shock Syndrome,Endotoxin Shocks,Shock Syndrome, Toxic,Shock, Endotoxin,Shocks, Endotoxin,Toxic Shock Syndromes