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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The insulin stimulatory effect of 7 mM glucose on isolated perifused rat islets is dramatically potentiated by the monokine interleukin 1 (IL-1). At levels (10(-10) -10(-8) M) noted in vivo during sepsis, it reversibly amplifies peak second phase insulin release to the hexose. At 2.75 mM glucose, however, IL-1 has no effect on insulin secretion. IL-1 also potentiates glyceraldehyde (2 mM)- and alpha-ketoisocaproate (5 mM)-induced insulin secretion. In islets whose phosphoinositides were prelabeled with myo-[2-3H]inositol, 2.0-5.0 nM IL-1 increases the efflux of [3H]inositol from subsequently perifused islets, the parallel accumulation of labeled inositol phosphates, and insulin secretion in the simultaneous presence of 7 mM glucose but not 2.75 mM glucose. In support of these in vitro observations, the in vivo infusion of IL-1 (40 micrograms/kg body wt) elevated circulating plasma insulin levels two-to fourfold. These results establish IL-1 as a potent, readily reversible, glucose-dependent modulator of stimulated insulin secretion and further suggest that its positive impact on insulin release is mediated, at least in part, by phosphoinositide-derived second messenger molecules. IL-1-induced insulin secretion may participate in the multiple metabolic and immunologic adaptations occurring during sepsis.
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PMID:Interleukin 1 is a potent stimulator of islet insulin secretion and phosphoinositide hydrolysis. 253 31

Inventarising the inflammatory capacities of the three types of inflammatory cells, PMN, macrophages and mast cells, each type seems able to induce a lethal whole body reaction. This whole body inflammation has hitherto largely escaped our attention, as in clinical studies inappropriate methods have been used such as counting peripheral leucocytes, and as monitoring key-mediators (IL-1, TNF, PGE-2, leukotrienes) and key-cells (activated PMN, macrophages and mast cells) hitherto was impossible. Presently a new set of methods is available, allowing a closer look at this whole body inflammation, such as elastase (monitoring PMN activity), neopterin (monitoring macrophage activity) and hopefully clinically practicable methods to monitor cytokines as well as endotoxin-levels. Only after such comprehensive studies have been performed, it might be concluded that--as in the experimental animal--sepsis and MOF may not necessarily be caused by bacteria or their endotoxins, but by an untoward autodestructive and self-sustaining activation of angry leucocytes and mad macrophages.
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PMID:Multiple organ failure: whole body inflammation? 265 70

A survey is given of the occurrence, the biochemical qualities and the various functions of macrophages. By binding of gamma-interferon and of waste products of bacteria they are activated and increasedly give off interleukin 1 and other compounds, which play a part in the evocation of the immune reaction and the inflammatory processes. The interleukin 1 causes the evocation of fever, an increase of the secretion of corticoliberin and of ACTH, an increase of the formation of the proteins which are increasedly effective in the acute phase of the inflammation as well as an activation of B- and T-lymphocytes. For the phagocytosis, among others, the fibronectin is of importance, the content of which in the blood plasma is greatly reduced in sepsis and after severe burns. In macrophages an elaboration of numerous antigens takes place which are then transferred into the membrane and under participation of glycoproteins of MCH II cause an activation of T-lymphocytes.
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PMID:[Some recent facts on the function of macrophages and their modification]. 265 17

Interleukin 1 has been implicated as a mediator of both systemic and local responses to infection and injury. Since systemic and local vasodilatation are hallmarks of sepsis and infection, we studied the direct effect of IL-1 on vascular contractility. We report here that human recombinant IL-1-beta potently inhibits the response of rat thoracic aorta to vasoconstrictor agents. Exposure of isolated rat aortic rings to IL-1 (20 ng/ml) for 1 h did not affect phenylephrine-induced contractions during the exposure period. However, when rings were retested 150-200 min after initiation of IL-1 exposure, contractions were markedly decreased. The cytokine had a similar effect in rings from which the endothelium was removed. Contractions caused by potassium depolarization also were depressed, indicating the effect of IL-1 is not specific to the alpha-adrenoceptor agonist. The inhibitory effect of IL-1 was concentration-dependent (0.2 to 20 ng/ml), and eliminated by pretreatment with cycloheximide (20 micrograms/ml). Indomethacin (10(-5) M) did not prevent the inhibition caused by IL-1. These studies identify IL-1 as a potent inhibitor of vascular contraction, via an endothelium-independent mechanism. Studies with inhibitors suggest that the action of IL-1 is independent of prostanoid synthesis, and may involve synthesis of protein.
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PMID:Interleukin 1 inhibits contraction of vascular smooth muscle. 278 26

Human peripheral adherent cells from splenectomized subjects, human spleen cells and mouse spleen cells were tested for IL-1 production in vitro in presence or absence of synthetic tuftsin (Thr-Lys-Pro-Arg). Application of synthetic tuftsin to peripheral blood adherent cells from normal donors as well as from splenectomized subjects induces IL-1 production. In splenectomized subjects the extent of induction was more evident than in controls. In human splenic cells tuftsin stimulates IL-1 production without KLH or LPS. In mouse spleen cells tuftsin alone did not stimulate the IL-1 secretion. However, addition of tuftsin to mouse spleen cells incubated with KLH augmented significantly the IL-1 secretion. As removal of the spleen leads to tuftsin deficiency, our present findings may perhaps explain the fulminant nature of the postplenectomy sepsis and some immune disturbances described in the postplenectomy state.
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PMID:Tuftsin stimulates IL-1 production by human mononuclear cells, human spleen cells and mouse spleen cells in vitro. 278 82

Single daily injections of recombinant human interleukin-1 alpha (IL-1 alpha) or interleukin-1 beta (IL-1 beta) were given for 1-3 days to normal mice, and blood ionized calcium concentrations were measured before and at various times after each injection. Mean blood calcium levels fell significantly in both groups of animals 3 h after the first IL-1 injections and returned to pretreatment values at 5 h. However, at 24 and 48 h mean values were significantly higher than those in saline-heated controls. Despite this progressive underlying increase in mean blood ionized calcium concentrations, blood calcium concentrations also fell significantly 3 h after the second and third IL-1 injections. The transient decrease in blood calcium was prevented by treatment with indomethacin and, thus, appears to be prostaglandin mediated. Hypocalcemia was not observed after single bolus injections of tumor necrosis factor-alpha or -beta (lymphotoxin). These findings suggest that IL-1 is a potential mediator of the hypocalcemia that occurs in up to 40% of patients with bacteremic sepsis and severe tissue injury and is associated with an increased mortality rate.
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PMID:Bolus injections of recombinant human interleukin-1 cause transient hypocalcemia in normal mice. 279 8

Alterations in macrophage function may render the immunocompromised host more susceptible to infectious complications. Although allograft recipients are at increased risk of infection primarily because of pharmacologic immunosuppression, whether the process of allosensitization per se alters this risk is unknown. We therefore studied the effects of cloned allosensitized murine helper or cytotoxic T cells on both interleukin 1 (IL-1) and prostaglandin E2 (PGE2) production by syngeneic resident murine peritoneal macrophages. Endotoxin (lipopolysaccharide [LPS]) stimulated both IL-1 and PGE2 production in macrophages. Cloned T cells alone, with or without LPS pretreatment, produced neither IL-1 nor PGE2. After 48 hours of coculture with LPS-treated macrophages, cloned helper cells augmented IL-1 release by macrophages but inhibited PGE2 production. In contrast, cytotoxic T cells not only reduced IL-1 production by macrophages but also potentiated PGE2 release. These effects were not observed when macrophages were not first exposed to LPS. Thus, endotoxin renders macrophages more susceptible to allosensitized "help" (increases IL-1, decreases PGE2) or "suppression" (decreases IL-1, increases PGE2) by cytotoxic T cells. We hypothesize that, even in the absence of immunosuppression, the process of allosensitization itself may modulate the response to sepsis by altering host macrophage function.
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PMID:Allosensitized helper and cytotoxic T-lymphocyte clones differentially modulate endotoxin-stimulated macrophage function. 296 2

Tumor necrosis factor/cachectin (TNF) has been implicated as a mediator of the host response in sepsis and neoplasia. Recent work has shown that TNF can modulate endothelial cell hemostatic properties, suggesting that endothelium is a target tissue for TNF. This led us to examine whether endothelial cells have specific binding sites for TNF and augment the biological response to TNF by elaborating the inflammatory mediator, IL-1. Incubation of 125I-recombinant human TNF with confluent, cultured human umbilical vein endothelial cells resulted in time-dependent, reversible, and saturable binding. Binding was half-maximal at a TNF concentration of 105 +/- 40 pM, and at saturation 1,500 molecules were bound per cell. Heat-treated TNF, which is biologically inactive, did not bind to endothelium. In addition to surface binding, TNF induced the elaboration of IL-1 activity by endothelial cells in a time-dependent manner. Generation of IL-1 activity required protein synthesis and was half-maximal at a TNF concentration of 50 +/- 20 pM. IL-1 activity from TNF-treated endothelium could be adsorbed by an immobilized antibody to IL-1. Heat-treated TNF was ineffective in eliciting endothelial cell IL-1. These data indicate that TNF can bind specifically to endothelium and initiate a cascade of inflammatory and coagulant events on the vessel surface potentially central to the host response to neoplasia and sepsis.
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PMID:Tumor necrosis factor/cachectin interacts with endothelial cell receptors to induce release of interleukin 1. 301 46

Tumor necrosis factor (TNF; cachectin) has been implicated as a mediator of the toxic manifestations of overwhelming bacterial infection as well as the chronic catabolic state of cancer cachexia. We have examined the acute metabolic and hormonal response after administration of recombinant human TNF in the rat. TNF given by intraperitoneal injection produced dose- and time-related increases in hepatic amino acid uptake, decreases in serum trace metal concentrations, and a pattern of endocrine hormone alterations characteristic of the acute phase response to tissue injury. In vitro zinc transport studies by rat hepatocytes cultured in the presence of TNF alone, or in combination with recombinant human interleukin 1, another mediator of the acute phase response, demonstrated that neither monokine was capable of directly stimulating zinc transport into cells. These findings suggest that TNF may function as an endogenous mediator of the early metabolic response to sepsis and that the trace metal changes induced by TNF in vivo may occur through a secondary mechanism.
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PMID:Hormonal and metabolic response to recombinant human tumor necrosis factor in rat: in vitro and in vivo. 304 39

It is not clear which factors are responsible for the deficient resistance of human neonates to K1 E. coli sepsis and meningitis. To evaluate the relative importance of different defense mechanisms against bacterial invasion, we have analyzed the sensitivity of newborn mice with known immune deficiencies to infection after oral challenge with virulent K1 E. coli. T and B lymphocyte and complement (C5) defects had no significant effect on natural resistance. In contrast, both endotoxin-hyporesponsive mouse strains tested were highly sensitive. This susceptibility to infection was strongly age dependent. Infant endotoxin-hyporesponsive mice were killed by i.p. injection of less than ten virulent K1 E. coli cells. In contrast, endotoxin-responsive animals and F1 hybrids derived from crosses between endotoxin-responsive and hyporesponsive mice survived an injection with up to 10(4) bacteria. Mutants of a virulent 018:K1 E. coli strain defective in the synthesis of the capsular polysaccharide or the O-antigen of lipopolysaccharide were avirulent as were 01:K1 bacteria, which are under-represented among E. coli isolates from neonatal meningitis. Endotoxin-hyporesponsive mice were protected from lethal bacterial challenge by monoclonal IgG specific for the O-antigen of the challenge strain or by human recombinant interleukin 1. A fulminant bacterial multiplication in the bloodstream of endotoxin-hyporesponsive mice was observed after i.v. injection of 100 virulent K1 E. coli cells. Persistent bacteremia with 10(5) to 10(6) bacteria per ml of blood resulted in death of the animals one to two days after challenge. In the bloodstream of endotoxin-responsive mice the bacteria proliferated to a comparable extent within the first 6 h after challenge. Thereafter they were rapidly cleared from the circulation and the animals recovered from the infection.
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PMID:Host factors in the resistance of newborn mice to K1 Escherichia coli infection. 305 39


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