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

Some disease processes in which increased endotoxin and cytokine levels exist (e.g., sepsis and infantile diarrhea) are also associated with increased levels of blood nitrates, the stable end products of nitric oxide. Available evidence suggests that the effects of an endotoxic environment, with its attendant complex cytokine networks, on liver function are mediated in part by modulation of hepatic nitric oxide synthesis. This hypothesis was tested by means of studying nitric oxide formation and its regulation in liver parenchymal and nonparenchymal cells of rats that had been continuously infused with endotoxin for 30 hr. Hepatocytes of such rats responded to in vitro stimulation for 20 hr by single cytokines, tumor necrosis factor, interleukin-1 beta and interferon-gamma with enhanced nitric oxide formation. In combination, interferon-gamma and endotoxin had greater synergistic effect on hepatocytes than did tumor necrosis factor and endotoxin. Kupffer cells of these endotoxic rats responded to 20 hr of interferon-gamma stimulation with the same enhanced nitric oxide formation we documented previously for endotoxin. Potentiation of the effect, through combination of endotoxin and interferon-gamma, was not as marked as it was with hepatocytes. Challenge of Kupffer cells with tumor necrosis factor or interleukin-1 beta evoked no response. Hepatocytes and Kupffer cells of time-matched, saline solution-treated rats were unresponsive to endotoxin or cytokine stimulation. Small quantities of nitric oxide were produced by endothelial cells spontaneously; this production was somewhat enhanced in cells of the endotoxin-infused rats by a 20-hr in vitro endotoxin challenge. Studies with inhibitors suggest that enhanced nitric oxide formation by endotoxic hepatocytes and Kupffer cells in response to in vitro endotoxin stimulation is differentially regulated. Our findings indicate modulation of nitric oxide generation by cytokines in vitro in various liver cell types of endotoxic rats. A similar scenario may exist in vivo because of the prevailing inflammatory response to endotoxin administration.
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PMID:Cytokine stimulation of nitric oxide formation and differential regulation in hepatocytes and nonparenchymal cells of endotoxemic rats. 827 58

A recombinant (r) NH2-terminal fragment of bactericidal/permeability-increasing protein, rBPI23, was shown to inhibit murine macrophage nitric oxide (NO) production elicited by lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma). Normal mouse plasma amplified NO synthesis (measured as NO2- release) at LPS concentrations of 1-10 ng/mL, and antibody to the plasma LPS-binding protein (LBP) partially inhibited NO2- release in the presence of normal mouse plasma. rBPI23 (1 microgram/mL) effectively inhibited LPS-dependent NO2- release in the presence or absence of normal mouse plasma. Fifty percent inhibition of IFN-gamma/LPS-elicited NO2- production or of binding of fluoresceinated LPS was obtained with approximately 0.2 microgram/mL rBPI23. These results provide a basis for studies of rBPI23 effects on NO synthase activity in murine models of gram-negative sepsis.
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PMID:Bactericidal/permeability-increasing protein inhibits induction of macrophage nitric oxide production by lipopolysaccharide. 827 72

The systemic inflammatory response syndrome (SIRS) is an acute illness characterized by generalized activation of the endothelium. The most severe form of the syndrome is found in patients with shock due to gram-negative sepsis. We examined both animal and limited human data for the contribution of cytokines to this syndrome. Cytokines are endogenously produced proteins of small molecular weight and multiple biological effects. The cytokines interleukin 1 (IL-1) and tumor necrosis factor (TNF), as well as interferon-gamma and interleukin 8, are discussed. Laboratory investigations suggest that these cytokines play a critical role in SIRS by promoting the biochemical and clinical characteristics of SIRS. The biochemical changes induced by TNF and IL-1 include increased synthesis of nitric oxide, prostaglandins, platelet-activating factor, and endothelial cell adhesion molecules. Specific blockade of TNF using neutralizing antibodies or soluble receptors to TNF in animal models of SIRS reduces mortality and severity of disease. Similar results have been observed blocking IL-1 using soluble IL-1 receptors or IL-1 receptor antagonists. Preliminary clinical studies suggest that blockade may be useful in treating human SIRS. The various strategies for blocking IL-1 and TNF are presented; in addition, their mechanism(s) of action and safety in humans are discussed. We conclude that based on animal studies and preliminary clinical trials, strategies to block IL-1 or TNF may benefit patients with the syndrome, although thorough clinical trials have not been completed.
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PMID:Anticytokine strategies in the treatment of the systemic inflammatory response syndrome. 845 16

Interleukin-10 (IL-10) is a potent regulator of proinflammatory cytokines, including tumor necrosis factor-alpha, IL-1, IL-6, and interferon-gamma. We retrospectively evaluated 66 severely injured patients for detectable plasma IL-10. the presence or absence of IL-10 was correlated with clinical parameters. Forty of 66 patients had detectable levels of IL-10. Plasma IL-10 was associated with admission hypotension (p < 0.01) and the development of sepsis (p < 0.05). There was no difference between IL-10-positive and -negative patients with respect to age, mechanism or severity of injury, blood transfusion, operative interventions, or the subsequent development of ARDS, hepatic dysfunction, or renal insufficiency. We conclude that IL-10 can be detected in the plasma of some severely injured patients and that it is associated with the development of sepsis. Further investigation of the immunoregulatory effects of IL-10 after trauma is indicated.
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PMID:Interleukin-10 is associated with the development of sepsis in trauma patients. 861 42

Massive hemorrhagic necrosis (MHN) of the liver following orthotopic liver transplantation (OLT) occurs infrequently during an otherwise uneventful recovery 1 week after OLT. It is characterized by fever and sudden deterioration of allograft function leading to failure in the absence of vascular thrombosis. The etiology is unknown, although it is usually preceded by some degree of allograft rejection. Between 6 and 8 days after OLT, four patients (out of 150) became febrile, hypotensive, and experienced a rapid rise in transaminases within 48 hr. Two patients had evidence of mild rejection; the other two had moderate to severe acute cellular rejection. All patients were ABO identical, crossmatch negative. Bolus steroids were given followed by OKT3 in the two patients with severe rejection. Although sepsis was suspected, antibiotic therapy did not ameliorate the clinical course. Each patient progressed to MHN with severe centrilobular necrosis and variable portal infiltrate. High levels of interferon-gamma and tumor necrosis factor-alpha occurred prior to the rise in transaminases in each MHN patient (155 +/- 39 pg/ml and 414 +/- 201 pg/ml, respectively) compared with levels in OLT patients with severe rejection (14 +/- 4 pg/ml and 26 +/- 5 pg/ml, respectively, P < 0.05). These data support the concept of a cytokine-mediated inflammatory response leading to a univisceral Shwartzman reaction in the transplanted liver. Early recognition of this syndrome and retransplantation are critical for survival.
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PMID:Early graft loss secondary to massive hemorrhagic necrosis following orthotopic liver transplantation. Evidence for cytokine-mediated univisceral Shwartzman reaction. 862 99

Newborn infants often suffer from bacterial and viral infections without presenting typical symptoms. Therefore, reliable methods for detecting and monitoring sepsis in the newborn would be beneficial. In older patients C-reactive protein (CRP) and neopterin have proved useful serum markers of infection and inflammation. Both of these markers are regulated by cytokines, and it has been proposed that cytokines themselves could be used to monitor immune activation and infection. This study has examined the levels of CRP, neopterin, soluble IL-2R, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in cord blood samples from both premature and term neonates. Having established reference ranges for these analytes, serial measurements were made in babies requiring intensive care support. The results suggest that in preterm infants the simultaneous measurement of CRP and neopterin, and possibly soluble IL-2R, may provide an accurate early diagnosis of sepsis and may be of use in differentiating between bacterial and viral etiologies. In addition, serial measurement of these markers may help in the early diagnosis of necrotizing enterocolitis (NEC).
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PMID:Inflammatory and immunological markers in preterm infants: correlation with disease. 880 48

Monocyte/T-cell interactions play a critical role in the systemic response to infection. Distinct patterns of cytokines are produced by two different types of T-helper cells (Th). Th1 cells secrete interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), whereas Th2 cells produce IL-4, IL-5, IL-6, IL-10, and IL-13. In volunteers systemic endotoxin administration initiates many features of gram-negative sepsis including cytokine release, but the patterns (i.e., Th1/Th2 patterns) have not yet been studied. In this institutional review board-approved study we investigated the effect of an intravenous bolus of endotoxin from Escherichia coli (4 ng/kg body weight) on the Th1/Th2 response in four female and four male volunteers (mean age 27.1 +/- 0.8 years). Plasma cytokine levels for IL-2, IL-4, IL-10, IL-12, and IFN-gamma and heart rate, mean arterial pressure, temperature, white blood cell, and differential blood count were determined before and hourly for 5 hours after endotoxin administration. All volunteers had tachycardia, decreased mean arterial pressure, fever, and leukocytosis. IL-10 was significantly (p < 0.05) elevated (9.4 +/- 3.9 pg/ml vs 60.9 +/- 19.3 pg/ml) 3 hours after endotoxin was administered, whereas IL-2 levels were decreased (69 +/- 26 U/ml vs 30.6 +/- 14.9 U/ml). IL-4 and IFN-gamma were not detectable in plasma. No changes were seen in the plasma levels of IL-12. Systemic responses did not correlate with changes in cytokine levels. Cytokine patterns found in this study suggest that after low-dose endotoxin administration the T-cell immune response is shifted towards the Th2 cell type response. This early shift towards a Th2 cell response may contribute to the depressed cell-mediated immune response associated with sepsis.
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PMID:The 1996 Moyer Award. Effects of endotoxin on the Th1/Th2 response in humans. 895 35

A review on the possible involvement of tumor necrosis factor-alpha (TNF) in cachexia is presented. While this cytokine is definitely linked to sepsis and tumor-associated weight loss in some experimental models, other cytokines, such as interleukin-6 (IL-6) or interferon-gamma (IFN-gamma), alone or in combination with TNF, may also play an important role in the development of cachexia.
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PMID:Is TNF really involved in cachexia? 902 89

Distinct cytokine profiles are clearly associated with and relate to the severity of several types of infections. Cytokine networks are apparent with selected human infectious diseases, such as mycobacterial infections (leprosy, tuberculosis), the parasitic infection leishmaniasis, human immunodeficiency virus (HIV) infection, and gram-negative sepsis. Cytokine profiles are determined to some extent by two functional subsets of T lymphocytes, Th1 and Th2. The Th1 cytokines (interferon gamma, interleukin-2 [IL-2], IL-12) enhance cell-mediated immunity, inhibit humoral immunity, and result in protective effect for pathogens that are removed primarily through cell-mediated immunity (Mycobacterium tuberculosis, Mycobacterium leprae, Leishmania). The Th2 cytokines (IL-4, IL-5, IL-10, IL-13) enhance humoral immunity and inhibit cell-mediated immunity, and result in protective effect for pathogens removed primarily through humoral mechanisms. Progression of HIV infection is associated with a switch from a Th1 to a Th2 profile. For sepsis, uncontrolled activation of proinflammatory cytokines (IL-1, tumor necrosis factor-alpha, interferon-gamma) may be a fundamental defect that promotes the detrimental aspects of inflammation, whereas Th2 cytokines may be beneficial in controlling inflammation. Knowledge of basic cytokine immunopharmacology, networks, and relationships with infectious processes will aid clinicians in determining treatment approaches that are likely to be effective.
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PMID:Cytokine networks with infection: mycobacterial infections, leishmaniasis, human immunodeficiency virus infection, and sepsis. 908 11

Lipopolysaccharides (LPS) of gram-negative bacteria and superantigens of gram-positive bacteria are among the main causes of sepsis and septic shock. Symptoms are initiated primarily by the release of endogenous mediators, especially cytokines. In the last few years, increasing evidence for the clinical relevance of mixed sepsis caused by coinfections with both types of bacteria has been found. Therefore, we developed an in vitro mixed sepsis model investigating the effect of different superantigen doses, in combination with different LPS concentrations, on cytokine production in human PBMCs using ELISA and RT-PCR. Low, in vivo relevant concentrations of the superantigen toxic shock syndrome toxin-1 (TSST-1) synergistically enhance LPS-induced production of interferon-gamma (IFN-gamma) interleukin-1 beta (IL-1 beta), IL-6, and IL-10, but low LPS has no comparable effect. Signal transduction studies with different inhibitors suggest that this one-way synergism is caused by an interaction between the cAMP and the PIP2 signaling pathway. Furthermore, our findings support the idea that this interaction is one important crossover point of signal transduction pathways by LPS and superantigens, which seems to be predominantly regulated by IFN-gamma and PGE-2. The identification of additional crossover points in the genesis of a mixed sepsis and their selective influence could lead to identical treatment of both gram-negative and gram-positive sepsis.
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PMID:One-way synergistic effect of low superantigen concentrations on lipopolysaccharide-induced cytokine production. 914 52


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