Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A single extra-amniotic injection of prostaglandin (PG) E2 or F2alpha in a highly viscous gel was administered to 230 patients to induce abortion between 9 and 24 weeks gestation. PGE2 doses of 1-0, 1-5, 2-0 or 3-0 mg induced abortion within 24 hours in 30 per cent, 75 per cent, 76 per cent and 70 per cent of patients respectively. The incidence of gastrointestinal side-effects was dose dependent, being 20 per cent, 35 per cent, 45 per cent and 70 per cent in the respective groups. A 10-0 Pmg dose of PGF2alpha induced abortion within 24 hours in 66 per cent of patients and 45 per cent had gastrointestinal side-effects. Abortion was more often complete with PGE2 (76 per cent) than with PGF2alpha (36 per cent). Immediate withdrawal of the catheter following PG administration did not influence induction-abortion intervals or 24-hour abortion success rates. This technique significantly reduced individual patient care and minimized the potential risk of intrauterine sepsis associated with extra-amniotic techniques requiring repeated or continuous PG administration.
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PMID:Single extra-amniotic injection of prostaglandins in viscous gel to induce abortion. 77 9

Prostaglandin E (PGE) has been hypothesized to be the endogenous metabolite that results in the immunosuppression seen in patients with tumor and trauma. This has resulted in multiple investigators proposing that administration of PGE inhibitors, such as aspirin and indomethacin, might improve immune function in such patients. We administered a long acting PGE analog, misoprostol, to nine normal healthy volunteers for five days and assayed immune function before and after therapy. The PGE analog improved lymphocyte blastogenesis and increased tumor necrosis factor production. The PGE analog also resulted in the volunteers having symptoms similar to those seen in patients with sepsis. The results of these studies indicate that elevated levels of PGE do not seem to result in impairment of immune function, but may be the endogenous metabolite responsible for the symptologic factors seen in infected patients.
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PMID:Effect of prostaglandin E on immune function in normal healthy volunteers. 141 90

We investigated the production of chemical mediators by hepatic macrophages from rats with sepsis and the modulation of hepatocyte function by these hepatic macrophages. The chemical mediators we measured were superoxide (O2-), TNF, IL-1, and PGE2. Production of these mediators by hepatic macrophages from rats with sepsis was significantly increased. Furthermore, protein synthesis by cultured hepatocytes was inhibited in a co-culture system of hepatocytes and hepatic macrophages from rats with sepsis, and it was even inhibited by the supernatant of cultured hepatic macrophages from septic rats. These results demonstrate that hepatic macrophages are activated in sepsis and may play a role in inducing hepatic dysfunction in sepsis.
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PMID:Enhancement and hepatocyte-modulating effect of chemical mediators and monokines produced by hepatic macrophages in rats with induced sepsis. 165

Stress reactions exist in many conditions in which plasma interleukin 6 (IL-6) is elevated. Examples are burns and sepsis. In these situations fever is often present. These stress situations are always accompanied with high levels of adrenalin and corticosteroids. These hormones, especially when given together, elicit a definite response of acute phase proteins in normal rats. In two stress models, (i) laparotomy and (ii) fever induced by administration of PGE2 in the lateral intracerebral ventricle, we observed a rise of adrenalin and corticosteron followed by an elevated level of plasma IL-6. Therefore, we studied the effect of adrenalin and corticosteron on the plasma level of IL-6. Adrenalin evokes high levels of IL-6, and this effect can be blocked by propranolol. When IL-6 release is blocked in this way, the response of alpha 2 macroglobulin and the cysteine protease inhibitor, both fast-reacting acute phase proteins in rat, is strongly depressed. Isoprenalin, an adreno beta 2 agonist, also causes very high levels of IL-6, indicating that the release of IL-6 can be mediated by an adreno beta 2 receptor whose presence has been demonstrated in monocytic cells. The results suggest a relation between stress situations and IL-6 and may be another factor besides the presence of endotoxins, virus, etc. explaining the high levels of IL-6 observed in many serious clinical situations.
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PMID:The relation among stress, adrenalin, interleukin 6 and acute phase proteins in the rat. 169 83

Hemorrhagic shock causes a severe suppression of cellular immunity and an increased susceptibility to sepsis that may be due to increased release of prostaglandin E2 by macrophages. Since chloroquine inhibits the secretion of prostaglandin E2 by macrophages in vitro, the effects of chloroquine administration in vivo following hemorrhagic shock on macrophage prostaglandin E2 secretion and on depressed cellular immunity were examined. Inbred C3H/HeN male mice, aged 6 to 8 weeks, were bled to a mean blood pressure of 35 mm Hg, which was maintained for 60 minutes, and adequately, resuscitated. Mice then received intramuscular injections of either saline (vehicle) or chloroquine (10 mg/kg of body weight). Prostaglandin E2 in macrophage supernatants (radioimmunoassay) concanavalin A-dependent splenocyte proliferation, and interleukin 2 in splenocyte supernatants (CTLL 20 interleukin 2-dependent proliferation) were determined 2 or 24 hours later. Hemorrhage caused a significant decrease of splenocyte proliferation (47%) and interleukin 2 release (49%) at 24 hours, while prostaglandin E2 secretion from macrophages was elevated at 2 hours. Chloroquine treatment attenuated depression of splenocyte functions and reduced prostaglandin E2 release. Furthermore, chloroquine treatment decreased the mortality of septic mice after hemorrhage to levels comparable with those of sham-operated mice. Thus, chloroquine may be a useful adjunct in the clinical setting for the treatment of shock-induced immunodepression and increased susceptibility to sepsis following hemorrhage.
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PMID:Chloroquine attenuates hemorrhagic shock-induced immunosuppression and decreases susceptibility to sepsis. 173 52

Although the cytokines tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6) are important mediators of hemodynamic, metabolic, and immunologic alterations in the host during sepsis, it is not known whether there is any association between the release of these cytokines and prostanoids during sepsis. Sepsis induced by cecal ligation and puncture in rats led to a persistent elevation (p less than 0.05) of plasma TNF until 10 hours, steadily increasing (p less than 0.05) IL-1 plasma levels, and enhanced (p less than 0.05) IL-6 plasma levels at all time points compared to the sham group. Prostaglandin E2 plasma levels were elevated (p less than 0.05) at 5 hours (153 +/- 29 pg/mL; control: 47 +/- 11 pg/mL) and 10 hours (96 +/- 16 pg/mL; control: 21 +/- 5 pg/mL). Prostaglandin E2 production by splenic macrophages (sM phi) from septic animals was increased (p less than 0.05) at 5 hours (9.1 +/- 2.2 ng/mL) and 10 hours (5.6 +/- 1.5 ng/mL) compared to controls (3.3 +/- 0.3 ng/mL at 5 hours; 1.3 +/- 1.3 ng/mL at 10 hours). Incubation of sM phi from septic animals with ibuprofen enhanced (p less than 0.05) IL-1 and TNF synthesis, while IL-6 production was reduced (p less than 0.05). These results indicate that the alterations in prostanoid release and elevated plasma prostanoids may regulate the release and consequently the circulating levels of cytokines during sepsis.
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PMID:The complex pattern of cytokines in sepsis. Association between prostaglandins, cachectin, and interleukins. 186 21

Tumor necrosis factor (TNF) is an important mediator of the systemic response to gram-negative sepsis and endotoxemia. We studied the renal effects of a sublethal TNF infusion in dogs (0.54 = 10(5) international units per kilogram of body weight during a six hour period). The TNF-infused dogs (n = 4) had marked polyuria and natriuresis in comparison with those in the control group (n = 12) (urine output, 35.3 +/- 4.1 versus 3.7 +/- 0.5 millimeters per kilogram per six hours p less than 0.01; sodium excretion, 2.82 +/- 0.27 versus 0.75 +/- 0.19, p less than 0.01). To evaluate the role of the spleen in this response, seven dogs that had splenectomy were infused with TNF. Splenectomy abolished both the polyuria and the natriuresis; this could not be explained by the differences in fluid balance or in hemodynamic or metabolic alterations. Treatment with ibuprofen given intravenously (12.5 milligrams per kilogram 40 minutes before and three hours after the beginning of TNF infusion) in eight dogs that did not undergo splenectomy also abolished these renal effects. Prostaglandin 2 (PGE2) concentrations in selected blood samples from the splenic vein did not increase with TNF infusion, excluding circulating PGE2 as a possible mediator of the renal effects. The results of these studies indicate that, during septic challenge or severe inflammation, the spleen participates in signaling the kidney to increase water and sodium excretion. These renal events are mediated through the cyclo-oxygenase pathway.
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PMID:Splenectomy attenuates the inappropriate diuresis associated with tumor necrosis factor administration. 190 Sep 57

Traumatic injury often results in profound immunopathology that can lead to immunosuppression, thereby increasing the morbidity and mortality due to sepsis. The isolation and partial characterization of an immunosuppressive glycopeptide (SAP) from serum of severely burned patients has previously been reported by our laboratory. Recently, this trauma peptide has also been identified in the serum of patients with multiple blunt trauma. This glycopeptide is capable of suppressing neutrophil chemotaxis, T-cell blastogenesis and the lysis of human erythrocytes. We demonstrate in this report that SAP inhibits interleukin 2 (IL-2) biosynthesis by mitogen-stimulated peripheral blood mononuclear cells. Peptide concentrations of 50 nmol and above significantly inhibited IL-2 production. Inhibition was not reduced by the addition of indomethacin or anti-PGE2 to cultures containing greater than 100 nmol of peptide, suggesting that inhibition is not entirely prostaglandin-mediated. Preliminary studies have shown that IL-2 suppression by SAP can be partially reversed by the addition of calcium ionophore. These results suggest a potential immunosuppressive mechanism of the trauma peptide in which T cell blastogenesis is inhibited by interference in IL-2 biosynthesis.
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PMID:In vitro inhibition of IL-2 biosynthesis in activated human peripheral blood mononuclear cells by a trauma-induced glycopeptide. 210 88

It is likely that dynamic interactions between hepatocytes and Kupffer cells contribute to the responses of these cell types both under normal conditions and during sepsis. In this study, we examined the influences of hepatocytes on the concentration of the inflammatory mediator PGE2 in Kupffer cell cultures. Evidence to suggest that cultured rat hepatocytes both metabolize PGE2 and produce a substance that promotes LPS-stimulated Kupffer cell PGE2 biosynthesis include the following: 1) PGE2 levels in Kupffer cell: hepatocyte coculture were lower than the levels in Kupffer cell cultures early after LPS stimulation; 2) 36 h after LPS, coculture PGE2 levels exceeded the levels in Kupffer cell cultures despite the demonstrated capacity for hepatocytes to metabolize PGE2; 3) a transferable, non-dialyzable, and heat-unstable factor in hepatocyte supernatant promoted PGE2 production when added to Kupffer cells with LPS or after LPS; 4) there was no increased PGE2 synthesis when the hepatocyte supernatant was added without LPS or if hepatocyte supernatant was preincubated with the Kupffer cells for 6 or 18 h before LPS administration; 5) there was an inability of the hepatocyte factor to promote PGE2 production in response to other macrophage-activating agents, including calcium ionophore A23187 or phorphol myristate acetate; and 6) there was no increased cell replication or protein synthesis in the Kupffer cell cultures following hepatocyte supernatant incubation. The increased Kupffer cell PGE2 production by the hepatocyte supernatant was not due to contamination of the hepatocyte supernatant by endotoxin or PGE2. These in vitro results raise the possibility that hepatocytes have the capacity to modulate local PGE2 levels by two distinct mechanisms. Hepatocytes can metabolize PGE2 as well as release factor(s) which promote LPS-induced PGE2 production by Kupffer cells.
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PMID:Hepatocyte modulation of Kupffer cell prostaglandin E2 production in vitro. 210 27

The present experiments were undertaken to elucidate the effect of either the hepatocyte (HC) or hepatocyte supernatant on prelabeled endotoxin (LPS)-stimulated Kupffer cell (KC) arachidonic acid utilization. HC, KC, or their coculture were incubated for 18 hours with labeled 1-14C- arachidonic acid followed by a 24 hour incubation with 10 micrograms/ml LPS. LPS had no effect on the percent distribution of labeled arachidonate into the HC phospholipid or neutral lipid. KC showed a decreased percent neutral lipid labeled arachidonic acid distribution with generally no effect on the phospholipid. However, KC:HC cocultures or the addition of HC supernatant to KC exposed to LPS dramatically reversed the labeled arachidonate distribution into the KC with an increased incorporation into neutral lipid. Labeled PGE2 and PGD2 were increased in the KC following incubation with HC supernatant while only labeled PGE2 levels were elevated in the cocultures. The changes in the distribution of cell's labeled arachidonate required the addition of LPS. These results suggest that the HC can promote changes in the lipid fraction during sepsis by elaborating a substance that can modulate labeled arachidonate distribution in the KC lipids as well as stimulate prostaglandin production.
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PMID:Kupffer cell-hepatocyte interactions and the changes in 1-14C-arachidonate incorporation in response to endotoxin in vitro. 211 70


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