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1.
Int J Mol Med ; 12(4): 565-70, 2003 Oct.
Article in English | MEDLINE | ID: mdl-12964035

ABSTRACT

The aim of this prospective cohort study was to address the feasibility of measuring cytokines in serum and urine as early predictor tests for the identification of septic Intensive Care Unit (ICU) patients. The study group consisted of 10 septic and 5 non-septic patients at the onset of sepsis according to modified definitions by the American College of Chest Physicians (ACCP)/Society of Critical Care Medicine (SCCM). Serum and urine samples were taken from septic patients at the onset of sepsis and from non-septic patients, every 12 h for 3 days and thereafter every 24 h until day 10. Levels of TNF-alpha, IL-1beta, IL-6, IL-10, IL-18, IFN-gamma, MCP-1, and PCT (procalcitonin) were measured by ELISA. Apart from serum IL-18 and PCT levels, which were elevated in septic patients (p<0.05), levels of all other cytokines and chemokines in the serum of septic patients did not exceed those of the control group. In urine, in contrast with TNF-alpha, IL-1beta, IL-6, IL-10, IFN-gamma, and MCP-1 in which no differences between the two groups were observed, a distinct trend of elevated IL-18 levels was observed only in the septic group. Whereas elevated serum IL-18 and PCT are clear candidate markers for sepsis criteria, the present data indicating elevated urine IL-18 levels albeit from a limited number of septic patients is an interesting observation. The profile of inflammatory mediators in serum and urine from septic patients herein warrants further investigations in a larger group of patients at the onset of sepsis driven by different infectious foci.


Subject(s)
Chemokines/blood , Chemokines/urine , Cytokines/blood , Cytokines/urine , Intensive Care Units , Sepsis/diagnosis , Adult , Aged , Calcitonin/blood , Calcitonin/urine , Calcitonin Gene-Related Peptide , Cohort Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Interleukin-18/blood , Interleukin-18/urine , Male , Middle Aged , Protein Precursors/blood , Protein Precursors/urine , RNA, Messenger/metabolism , Sepsis/blood , Sepsis/urine , Time Factors
2.
Int J Mol Med ; 11(1): 41-4, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12469215

ABSTRACT

The stimulatory effects of different purified lipopolysaccharide (LPS) preparations from E. coli, S. typhosa, P. aeruginosa, and K. pneumoniae on cytokine and chemokine production were measured in whole blood assays by ELISA. Incubation of 0.5 ml whole blood with 10 ng/ml E. coli and S. typhosa resulted in a time-dependent production of TNF-alpha, IL-1beta, IFN-gamma, IL-10 and MCP-1. K. pneumoniae, however, showed preferential effects on IL-1beta, IL-10 and MCP-1 production with less potent effects on TNF-alpha and IFN-gamma. LPS derived from P. aeruginosa showed a similar potency to other LPS preparations on MCP-1 production, yet completely failed to elicit the production of other cytokines. To further investigate potencies of the different LPS preparations, mediator production was determined following stimulation with agonist concentrations of 0.1 ng and 1000 ng per ml over a 24 h time period. Dose-response curves were obtained with LPS derived from E. coli, S. typhosa and K. pneumoniae on all mediators apart from IL-1beta and MCP-1. Most strikingly though, was the ability of LPS derived from P. aeruginosa to selectively elicit a significant dose-response effect on MCP-1 production, despite its very weak stimulatory effects on all other cytokines. These data imply that the bacterial origin of different LPS preparations can exhibit disparate effects on inflammatory mediator production. Furthermore, the potent, selective dose-response effect of P. aeruginosa LPS on MCP-1 production could help to explain the preponderance of a relentless inflammatory cellular infiltrate in diseases such as cystic fibrosis (CF).


Subject(s)
Chemokines/blood , Cytokines/blood , Lipopolysaccharides/pharmacology , Cytokines/drug effects , Dose-Response Relationship, Drug , Escherichia coli , Humans , Klebsiella pneumoniae , Lipopolysaccharides/isolation & purification , Male , Pseudomonas aeruginosa , Reference Values , Salmonella typhi
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