scholarly journals Tumor necrosis factor alpha in cerebrospinal fluid during bacterial, but not viral, meningitis. Evaluation in murine model infections and in patients.

1988 ◽  
Vol 167 (5) ◽  
pp. 1743-1748 ◽  
Author(s):  
T P Leist ◽  
K Frei ◽  
S Kam-Hansen ◽  
R M Zinkernagel ◽  
A Fontana

To evaluate the potential role of cachectin/TNF-alpha in the pathogenesis of bacterial and viral meningitis, concentrations and kinetics of TNF-alpha were determined in cerebrospinal fluid (CSF). After intracerebral, but not systemic, infection with Listeria monocytogenes in mice, TNF-alpha was detected as early as 3 h after infection reaching maximum titers after 24 h. However, TNF-alpha was not found in serum during the course of Listeria infection. In contrast to bacterial meningitis, no TNF-alpha was detected at any time in CSF of mice suffering from severe lymphocytic choriomeningitis induced by intracerebral infection with lymphocytic choriomeningitis virus. This difference is striking since both model infections led to a massive infiltration of polymorphonuclear and mononuclear leukocytes into the meninges and CSF. The results found for the two model infections were paralleled by findings in humans; CSF from three out of three patients with bacterial meningitis examined during the first day of hospitalization showed significant levels of TNF-alpha; none of the CSF obtained later than 3 d after hospitalization was positive. In addition, similarly to what was found in mice with viral meningitis, zero out of seven patients with viral meningitis had detectable TNF-alpha in CSF.

1996 ◽  
Vol 42 (5) ◽  
pp. 670-674 ◽  
Author(s):  
M Cruz Ruiz ◽  
F Recio Quijano ◽  
L F López Cortés ◽  
M Hebles Duvison ◽  
R Vázquez Rubio

Abstract The cytokine rumor necrosis factor-alpha (TNF-alpha) plays a prominent role in the inflammatory response and has been quantified in several kinds of body fluids. A safe method for keeping samples under the best storage conditions for later studies is clearly needed. We estimated TNF-alpha shelf life by using an accelerated stability testing protocol based on the Arrhenius equation. We investigated two kinds of samples: cerebrospinal fluid (CSF) normal pool (from patients without meningitis) and CSF pathological pool (from patients with pyogenic meningitis). Results of the stress protocol indicated that storing both normal and pathological CSF samples at -70 degrees C would maintain sample stability-i.e., retain at least 90% of the original TNF-alpha content-for approximately 5 years. At -20 degrees C and 4 degrees C, the projected stability time at which the same recovery would be obtained was 190 and 90 days, respectively.


Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3175-3181
Author(s):  
SJ McFaul ◽  
PD Bowman ◽  
VM Villa ◽  
MJ Gutierrez-Ibanez ◽  
M Johnson ◽  
...  

Incubation of human mononuclear leukocytes (MNL) with human stroma-free hemolysate (SFH), purified adult hemoglobin Ao (HbAo), and oxidized HbAo (METHb) caused MNL to release compounds into the supernate that mediated neutrophil (polymorphonuclear leukocytes, PMN) chemotaxis and PMN adherence to human umbilical vein endothelial cells (HUVEC). Chemotaxis and PMN adherence to HUVEC were reduced significantly when supernates were preincubated with neutralizing antibodies to interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-alpha), respectively, suggesting that IL-8 and TNF-alpha played significant roles in mediating these activities. Greatest chemotactic activity was observed in supernates of MNL treated with HbAo; while greatest PMN/endothelial cell (EC) adherence activity was observed in supernates of MNL treated with METHb. Furthermore, PMN/EC adherence activity was a function of METHb content in each hemoglobin solution. PMN chemotaxis, PMN adherence to HUVEC, and cytokine release increased as a function of increasing incubation time. Chemotactic activity was detected in HbAo- treated and METHb-treated MNL supernates after incubation for 6 hours and was maximal by 10 hours. IL-8 was detected in both HbAo and METHb- MNL supernates by 4 hours. PMN/EC adherence activity was detected in HbAo-MNL supernates at 10 hours and in METHb-MNL supernates at 4 hours. TNF-alpha was detected in METHb and HbAo-MNL supernates at 4 and 12 hours, respectively. These results suggest that hemoglobin solutions stimulate MNL to release IL-8 and TNF-alpha in quantities sufficient to induce PMN chemotaxis and PMN adherence to HUVEC. This is a US government work. There are no restrictions on its use.


Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3175-3181 ◽  
Author(s):  
SJ McFaul ◽  
PD Bowman ◽  
VM Villa ◽  
MJ Gutierrez-Ibanez ◽  
M Johnson ◽  
...  

Abstract Incubation of human mononuclear leukocytes (MNL) with human stroma-free hemolysate (SFH), purified adult hemoglobin Ao (HbAo), and oxidized HbAo (METHb) caused MNL to release compounds into the supernate that mediated neutrophil (polymorphonuclear leukocytes, PMN) chemotaxis and PMN adherence to human umbilical vein endothelial cells (HUVEC). Chemotaxis and PMN adherence to HUVEC were reduced significantly when supernates were preincubated with neutralizing antibodies to interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-alpha), respectively, suggesting that IL-8 and TNF-alpha played significant roles in mediating these activities. Greatest chemotactic activity was observed in supernates of MNL treated with HbAo; while greatest PMN/endothelial cell (EC) adherence activity was observed in supernates of MNL treated with METHb. Furthermore, PMN/EC adherence activity was a function of METHb content in each hemoglobin solution. PMN chemotaxis, PMN adherence to HUVEC, and cytokine release increased as a function of increasing incubation time. Chemotactic activity was detected in HbAo- treated and METHb-treated MNL supernates after incubation for 6 hours and was maximal by 10 hours. IL-8 was detected in both HbAo and METHb- MNL supernates by 4 hours. PMN/EC adherence activity was detected in HbAo-MNL supernates at 10 hours and in METHb-MNL supernates at 4 hours. TNF-alpha was detected in METHb and HbAo-MNL supernates at 4 and 12 hours, respectively. These results suggest that hemoglobin solutions stimulate MNL to release IL-8 and TNF-alpha in quantities sufficient to induce PMN chemotaxis and PMN adherence to HUVEC. This is a US government work. There are no restrictions on its use.


2005 ◽  
Vol 63 (1) ◽  
pp. 7-13 ◽  
Author(s):  
Vera Lúcia Jornada Krebs ◽  
Thelma Suely Okay ◽  
Yassuhiko Okay ◽  
Flávio Adolfo Costa Vaz

OBJECTIVE: To analyze the usefulness of determining the cerebrospinal fluid(CSF) levels of tumor necrosis factor-alpha(TNF-alpha),interleukin-1beta(IL-1beta) and interleukin-6(IL-6)for the early diagnosis and evaluation of the prognosis of neonatal meningitis. METHOD: We studied 54 newborn that underwent lumbar puncture.Thirty patients had meningitis and 24 were the control group.CSF and sera were obtained at the moment of suspicion of meningitis and stored at -70(0)C.Cytokines were performed by enzyme-linked immunosorbent assay method. RESULTS: CSF cytokines were detected in all the newborn with meningitis.TNF-alpha was detected in the CSF in 63.3% of the neonates, IL-1beta in 73.3% and IL-6 in 96.6%.The CSF levels were significantly higher than serum in neonates with meningitis.There was no correlation between the CSF levels of cytokines and neurologic complications. CONCLUSION: The detection of TNF-alpha, IL-1beta and IL-6 in the CSF is of great value in order to achieve a early diagnosis of neonatal meningitis.Among the three cytokines analyzed, IL-6 was the best indicator of meningeal inflammation.


1999 ◽  
Vol 67 (5) ◽  
pp. 2071-2074 ◽  
Author(s):  
Carl Granert ◽  
Johan Raud ◽  
Anders Waage ◽  
Lars Lindquist

ABSTRACT The inflammatory response in bacterial meningitis is mediated by cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-1 (IL-1), which are produced in the subarachnoid space by different cells, e.g., leukocytes, astrocytes, and microglia. The recruitment of leukocytes into the cerebrospinal fluid (CSF) has been shown to contribute to the neurological damage in this disease, a process which could be enhanced by treatment with antibiotics. In this study, we have used a rabbit meningitis model for two sets of experiments with intracisternal (i.c.) injections ofStreptococcus pneumoniae. First, pneumococcal cell wall (PCW) components were injected i.c., inducing an inflammatory response with pleocytosis and increased levels of CSF TNF-α) and IL-1 at 6 and 12 h after PCW injection. Treatment with fucoidin, known to inhibit leukocyte rolling, abolished pleocytosis and inhibited the release of TNF-α and IL-1. In the second experiment, live pneumococcal bacteria were injected i.c. and treatment with one dose of ampicillin (40 mg/kg of body weight intravenously) was given 16 h after induction of meningitis, causing a sevenfold increase in CSF leukocytes over a 4-h period. CSF IL-1 levels at 16 h were high but did not increase further at 20 h. Also, CSF TNF-α levels were high at 16 h and tended to increase at 20 h. Fucoidin treatment prevented the antibiotic-induced increase of CSF leukocytes but had no effect on the TNF-α and IL-1 levels. Taken together, fucoidin reduced CSF TNF-α and IL-1 levels in acute bacterial meningitis induced by PCW fragments but had no effect later in the course of the disease, when live bacteria were used and an inflammatory increase was caused by a dose of antibiotics.


2018 ◽  
Vol 69 (7) ◽  
pp. 1830-1837
Author(s):  
Cristian Nicolescu ◽  
Alaxendru Pop ◽  
Alin Mihu ◽  
Luminita Pilat ◽  
Ovidiu Bedreag ◽  
...  

This article presents an observational randomized prospective study done on 65 patients, who underwent major surgical interventions in the field of orthopedic surgery-total hip replacement or general surgery � total colectomy. The level of albuminemia in these cases were determined before the surgical intervention, after 6 hours of the intervention and after 24 h of the intervention. The measurements of the plasmatic concentration of the pro-inflammatory cytokines Tumor Necrosis factor -alpha (TNF-alpha) and interleukin 6 (IL6) were simultaneously done with the determination of the plasmatic levels of albumin. Values of hemoglobin and hematocrit were determined 24 h after the surgical procedure in order to exclude hemodilution, which could lead to a possible drop in the levels of plasmatic albumin. After the collection of the data, the statistical work was done and it consisted of descriptive statistics, correlation and comparison tests as well as statistical validation tests. Obtained results indicate that IL-6 plays a major role comparatively with that of TNF-alfa, regarding the decrease of the plasmatic level of albumin, and due to this, the primordial cause for hypoalbuminemia is an acute hepatic phase reaction. Supplemental permeability of the capillary wall under the action of TNF alpha has a secondary role, but could lead to a faster decrease in plasmatic albumin in the first hours after the surgical procedure.


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