Sex steroids enhance endotoxin-stimulated phospholipase A2 activity in hum endometrial cells

Summary Growing evidence suggests an association between intra-amniotic infection and preterm labor. We recently demonstrated that some factor(s) including endotoxin produced by the organism stimulated endogenous phospholipase A₂ resulting in liberation of arachidonic acid and prostaglandin formation (Takahashi et al. 1988). The studies presented in this report were designed to evaluate whether ovarian steroids alter activity of the phospholipase A₂ responsive to endotoxin. Exposure of human endometrial proliferative- or secretory-phases epithelium to endotoxin fromEscherichia coli increased the level of lysophosphatidylcholine (lyso-PC) by 15- and 25-fold, respectively. When the endometrial cells were preincubated with progesterone alone or progesterone and estradiol-17β for 16 h, the increase of lyso-PC by endotoxin was enhanced by approximately 1.5-fold. Progesterone showed a stimulatory effect on the response of phospholipase A₂ to bacterial endotoxin in endometrial cells. These observations may explain the mechanism(s) by which preterm or term labor associated with intra-amniotic infection is initiated.     

Interactions of Endotoxin with Cortisol and Acute Phase Proteins in Septic Shock Neonates

ABSTRACT. CRP, α1-acid glycoprotein and haptoglobin were studied in 13 septic shock neonates. Endotoxin was recovered from eight infants. Serum Cortisol concentration from infants with en-dotoxemia (917 ± 596 ng/ml) was significantly higher than that from infants without en-dotoxemia (398 ± 239 ng/ml). Serum Cortisol correlated well with immature neutrophil counts denned as the unit "band/neutrophil". Increased Cortisol level and immature neutrophil counts preceded the elevation of CRP, α1-acid glycoprotein and haptoglobin in four extremely premature neonates. We conclude that positive interactions between endotoxin, Cortisol and acute phase protein synthesis are present in the initial period of infection, and delayed acute phase protein synthesis is suspected in extremely premature neonates.     

The effect of immune enhancement and suppression on the development of laparoscopic port site metastasesrid=""id=""Presented at the 6th World Congress of Endoscopic Surgery, Rome, Italy, June 1998

Background: Recent clinical case reports and experimental studies have suggested that laparoscopic cancer surgery is associated with an increased risk of tumor spread to abdominal wall wounds. While the etiology of this problem was initially believed to be related to mechanical contamination of wounds, it is now recognized that there are other contributory factors, including disturbed immune function within the peritoneal cavity. To investigate this question further, we evaluated the effect of immune modulation within an established laparoscopic cancer model. Methods: Eighteen immune-competent syngeneic rats underwent modulation of their immune system, followed 18 h later by laparoscopy with the introduction of a suspension of adenocarcinoma cells into the peritoneal cavity. Rats were randomly allocated to receive either systemic cyclosporin (immune suppresser), intraperitoneal endotoxin (immune enhancer), or no agent (controls). Seven days later, all rats were killed and their peritoneal cavity was inspected for tumor implantation and port site metastases. Results: Cyclosporin did not influence the study outcome, but tumor growth (p= 0.008) and port site metastases (p < 0.0001) were less common following the administration of intraperitoneal endotoxin. Conclusion: The results of this study suggest that the immune system plays a role in the genesis of port site metastases. A preventive role for endotoxin in patients undergoing laparoscopic cancer surgery, however, remains speculative. Received: 22 July 1998/Accepted: 23 June 1999     

Chromogenic endotoxin determination in blood — clinical relevance

Summary In a pilot study in 400 patients LPS-quantification in blood using chromogenic substrates, bacterial cultures and bacterial quantification were performed. Decreased plasma levels of antithrombin III and plasminogen were early predictors of gram-negative septicemia, which already were apparant 3 days prior to the first positive LPS-test. It is concluded that daily determinations of LPS may reduce the delay in proper antibiotic therapy.     

Effects of two bacterial products,muramyl dipeptide and endotoxin,on bone resorption in organ culture

Summary We have compared two components of bacterial cell walls, muramyl dipeptide (MDP) and lipopolysaccharide (LPS), for their effects on bone resorption as measured by the release of previously incorporated⁴⁵Ca. MDP is the smallest active component of peptidoglycan, whereas LPS is the active component of endotoxin. Fetal rat long bones were cultured for 5 days in a chemically defined medium supplemented with bovine serum albumin (BSA) or serum. LPS increased⁴⁵Ca release at concentrations of 0.03–1.0 μg/ml. LPS further purified by electrolytic dialysis (ED-LPS) was active at 0.01 μg/ml. ED-LPS was ineffective at such low concentrations in the presence of serum. The response to MDP was more variable than that to LPS, but bone resorption was stimulated at concentrations of 10⁻⁷–10⁻⁵ M. MDP was less effective or inactive in medium supplemented with serum. Stereoisomers of MDP that do not have adjuvant activity caused minimal stimulation of bone resorption, whereas 6-0-steroyl MDP stimulated resorption at 10⁻⁸ M. The stimulation of bone resorption by LPS and MDP was not inhibited by indomethacin. Both LPS and MDP increased lysosomal enzyme release in proportion to their effects on⁴⁵Ca release. LPS also markedly increased collagenase activity in the medium, but MDP did not. These results indicate that chemically different products of bacterial cell walls can stimulate bone resorption in vitro. These products may be distinguished by differences in dose response curve, serum inhibition, and collagenase release. Part of this work was presented at the 2nd Annual Meeting of the American Society for Bone and Mineral Research, Washington, D.C., June 1980 [1].     

Hypothalamic opioids and the acute-phase glycoprotein response in guinea pigs

Endogenous opioids (EO) probably do not modulate endotoxin (LPS)- or interleukin 1 (IL1)-induced fever because naloxone does not prevent its development. Yet, increases in CSF and hypothalamic levels of beta-endorphin have been reported during LPS-and IL1-induced fevers. Since IL1 also reduces the specific binding of opioids to their receptors in guinea pig brain, the opioids could be involved in modulating nonfebrile effects of IL1. To determine whether EO might have a role in the IL1-induced acute-phase glycoprotein response of guinea pigs, (1) naloxone (5 and 10 mg/kg, SC) was injected prior to LPS (S. enteritidis 2 micrograms/kg, IV; N = 5), and (2) morphine (MOR, 10 micrograms/microliter), [D-ala2]-met-enkephalinamide (DAME, 5 micrograms/microliter), or dynorphin A (DYN, 5 micrograms/microliter) was injected into the preoptic area (1 microliter, bilaterally; N = 8/treatment) or into the 3rd ventricle (N = 4/treatment); pyrogen-free saline was the control injection. Measurements were: core temperature (Tco) and, as indices of acute-phase glycoproteins, plasma levels of copper (Cu) and N-acetylneuraminic acid (NANA). Naloxone did not prevent the fever or the increases in plasma Cu and NANA levels evoked by LPS. The intracerebral administration of opioid agonists by either route induced variable rises in Tco, each with a different pattern, but no increases in plasma Cu and NANA levels. Thus, EO do not participate in the central modulation of acute-phase glycoprotein synthesis, but may have a role in influencing other nonthermal IL1 effects in the CNS.     

84. Endotoxinschock: Erkennung und Behandlung

Zusammenfassung Der Endotoxinschock ist die häufigste Form des septischen Schocks. Endotoxin, ein makromolekulares Lipopolysaccharid wird beim Zerfall aus der Zellwand der gramnegativen Keime freigesetzt. Bei Patienten mit bakterieller Peritonitis sind: Fieber über 38°C, Thrombocytopenie, Leukocytose, Lactacidose, Kreatininanstieg hinweisende Zeichen. Die Frühlaparotomie ist bei bakterieller Peritonitis der entscheidende Schritt zur Vermeidung eines Endotoxinschocks.     

Biological reactions resulting from endotoxin adsorbed on dialysis membrane: an in vitro study

Some types of dialysis membrane are known to adsorb endotoxin (ET). It is suggested that the biocompatibility of dialysis membrane is enhanced by adsorption and inhibition of ET. This study attempts to clarify the membrane-mediated biological reaction of the ET that is adsorbed to a dialysis membrane. After a dialysis circuit was prepared, contaminated dialysate was introduced on the dialysate side of a polyether polymer alloy (PEPA) membrane that adsorbs ET while saline solution or blood were introduced on the blood side, and the difference in ET adsorption between the two set-ups was measured. Further, the side filled with blood was left standing for 2 h, after which the changes in the amount of interleukin 1 receptor antagonist (IL-1Ra) produced from the whole blood were also assayed. Significantly more ET was adsorbed to the dialysis membrane when blood rather than saline was on the other side. In addition, the IL-1Ra production from the dialysis membrane that adsorbed ET was significantly higher. The ET adsorbed to the dialysis membrane may influence a living body even if it does not pass through the membrane. Accordingly, it is difficult to assume that the adsorption of ET to the membrane enhances its biocompatibility.     

Developing ovarian follicles inhibit the endotoxin-induced glomerular inflammatory reaction in pseudopregnant rats

PROBLEM: We tested the hypothesis that developing ovarian follicles produce factors inhibiting the endotoxin induced inflammatory response. METHOD OF STUDY: Pseudopregnant rats were treated with FSH to induced follicular development (FSH-rats). For control we used untreated pseudopregnant rats (PSP-rats) and rats in the follicular phase of the ovarian cycle (C-rats). All rats were infused with either saline or endotoxin. Three days after the infusion rats were sacrificed and kidney specimens were snapfrozen. Cryostat kidney sections were stained for the presence of monocytes, granulocytes, CD11a- and CD11b-positive cells and for ICAM-1 expression. RESULTS: The results show that induction of follicular development in pseudopregnant rats inhibited glomerular infiltration of monocytes and CD11b(+) cells, while it did not affect the other parameters, i.e. glomerular granulocyte number, CD11a(+) cells and glomerular ICAM-1 expression. CONCLUSION: Developing ovarian follicles produce factors inhibiting monocyte responses to endotoxin.