Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lymphotoxin alpha (LT-alpha) and lymphotoxin beta (LT-beta) are members of the tumour necrosis factor (TNF) ligand family. Because of the importance of TNF in the pathogenesis of septic shock, the expression of LT-alpha and LT-beta mRNA in murine splenocytes stimulated with different pro-inflammatory cytokines, sepsis-associated mediators such as lipopolysaccharide (LPS) and bacterial superantigens was investigated. The authors show that the bacterial superantigens, toxic shock syndrome toxin 1 (TSST-1) and staphylococcal enterotoxin B (SEB) upregulate LT-alpha mRNA expression in vitro in murine cells. Basal expression of LT-beta mRNA was found in unstimulated murine splenocytes, and could be increased by the addition of the mitogen concanavalin A (Con A). Despite this suggested inducibility of the murine LT-beta transcript, sepsis-associated mediators did not affect its regulation. Neither the pro-inflammatory cytokines interleukin 2 (IL-2), TNF-alpha nor LPS alone or in combination with interferon gamma (IFN-gamma) had any effect on LT-beta mRNA expression. The bacterial superantigens TSST-1, SEB and streptococcal pyrogenic exotoxin A (SPEA) were also unable to upregulate LT-beta mRNA transcript, in contrast to the observation with LT-alpha.
 ...
PMID:The role of lipopolysaccharide, pro-inflammatory cytokines and bacterial superantigens in the transcriptional regulation of lymphotoxin alpha and beta in mouse splenocytes. 1004 17

Sepsis induces lymphocyte apoptosis and prevention of lymphocyte death may improve the chances of surviving this disorder. We compared the efficacy of a selective caspase-3 inhibitor to a polycaspase inhibitor and to caspase-3-/- mice. Both inhibitors prevented lymphocyte apoptosis and improved survival. Caspase-3-/- mice shared a decreased, but not total, block of apoptosis. The polycaspase inhibitor caused a very substantial decrease in bacteremia. Caspase inhibitors did not benefit RAG-1-/- mice, which had a > tenfold increase in bacteremia compared to controls. Adoptive transfer of T cells that overexpressed the anti-apoptotic protein Bcl-2 increased survival. T cells stimulated with anti-CD3 and anti-CD28 produced increased interleukin 2 and interferon gamma by 6 h. Thus, caspase inhibitors enhance immunity by preventing lymphocyte apoptosis and lymphocytes act rapidly, within 24 h, to control infection.
 ...
PMID:Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte. 1110 71

Infection is a leading cause of neonatal morbidity and mortality worldwide. Premature neonates are particularly susceptible to infection because of physiologic immaturity, comorbidity, and extraneous medical interventions. Additionally premature infants are at higher risk of progression to sepsis or severe sepsis, adverse outcomes, and antimicrobial toxicity. Currently initial diagnosis is based upon clinical suspicion accompanied by nonspecific clinical signs and is confirmed upon positive microbiologic culture results several days after institution of empiric therapy. There exists a significant need for rapid, objective, in vitro tests for diagnosis of infection in neonates who are experiencing clinical instability. We used immunoassays multiplexed on microarrays to identify differentially expressed serum proteins in clinically infected and non-infected neonates. Immunoassay arrays were effective for measurement of more than 100 cytokines in small volumes of serum available from neonates. Our analyses revealed significant alterations in levels of eight serum proteins in infected neonates that are associated with inflammation, coagulation, and fibrinolysis. Specifically P- and E-selectins, interleukin 2 soluble receptor alpha, interleukin 18, neutrophil elastase, urokinase plasminogen activator and its cognate receptor, and C-reactive protein were observed at statistically significant increased levels. Multivariate classifiers based on combinations of serum analytes exhibited better diagnostic specificity and sensitivity than single analytes. Multiplexed immunoassays of serum cytokines may have clinical utility as an adjunct for rapid diagnosis of infection and differentiation of etiologic agent in neonates with clinical decompensation.
 ...
PMID:Identification of diagnostic biomarkers for infection in premature neonates. 1862 29

Septic shock is the 13th leading cause of death in the United States. The rate of severe sepsis nearly doubled and mortality increased more than 60% during the 10-year period ending in 2003. Systemic inflammatory response syndrome has noninfectious and infectious causes. Noninfectious ones include burns, trauma, severe pancreatitis, and therapy with monoclonal antibodies or immunomodulatory drugs such as interleukin 2. Progression from sepsis syndrome to septic shock is caused by a series of immune responses. As an infectious injury progresses, host activation of the coagulation, immunological, and stress response systems ensues, resulting in tissue hypoperfusion and organ failure. Early studies with small numbers of patients suggest that treatment with low-dose corticosteroids has marked beneficial effects on shock reversal, the immune system, and the hemodynamic profile. Low-dose corticosteroids should only be administered to a subset of patients with septic shock who are unresponsive to fluid replacement and vasopressor therapy.
 ...
PMID:Low-dose corticosteroids to treat septic shock: a critical literature review. 2213 28

T cell suppression in sepsis is a well-known phenomenon; however, the underlying mechanisms are not fully understood. Previous studies have shown that T cell stimulation up-regulates mitochondrial adenosine triphosphate (ATP) production to fuel purinergic signaling mechanisms necessary for adequate T cell responses. Here we show that basal mitochondrial ATP production, ATP release, and stimulation of P2X1 receptors represent a standby purinergic signaling mechanism that is necessary for antigen recognition. Inhibition of this process impairs T cell vigilance and the ability of T cells to trigger T cell activation, up-regulate mitochondrial ATP production, and stimulate P2X4 and P2X7 receptors that elicit interleukin 2 production and T cell proliferation. T cells of patients with sepsis lack this standby purinergic signaling system owing to defects in mitochondrial function, ATP release, and calcium signaling. These defects impair antigen recognition and T cell function and are correlated with sepsis severity. Pharmacological targeting of these defects may improve T cell function and reduce the risk of sepsis.
...
PMID:Mitochondrial Dysfunction, Depleted Purinergic Signaling, and Defective T Cell Vigilance and Immune Defense. 2615 May 46

BACKGROUND Sarcoidosis is a systemic inflammatory disorder characterized by a classic pathologic feature of non-caseating granulomas involving any organ system. Hemophagocytic lymphohistiocytosis (HLH) is a catastrophic cytokine surge characterized by dysregulation of the macrophage response, which can be rapidly fatal. Recognition of HLH has been increasing over the past decade. HLH can present with features of sepsis that can make the diagnosis challenging and requires high clinical suspicion. CASE REPORT We report a case of a 48-year-old African American male with a past medical history of sarcoidosis infiltrating the lymph nodes, liver, and bone marrow with initial presentation of abdominal pain, nausea, vomiting, and weight loss of 100 pounds over 8 months. Sepsis was suspected, but the patient clinically deteriorated with vancomycin and cefepime. Fevers, bone marrow biopsy, anemia, thrombocytopenia, elevated ferritin, and elevated soluble receptor interleukin 2 confirmed HLH. The patient was treated with etoposide and dexamethasone with poor response and died from cardiac arrest. CONCLUSIONS Sarcoidosis associated with HLH is an extremely rare phenomenon with only 10 cases reported in the literature. Early clinical suspicion can be challenging as this condition is a sepsis-mimicker. To reduce mortality, prompt initiation of therapy is a key determinant in patients who are clinically deteriorating despite treatment for sepsis.
 ...
PMID:A Rare and Fatal Case of Hemophagocytic Lymphohistiocytosis Associated with Sarcoidosis. 3231 94


<< Previous 1 2