Blood components influence cytokine induction by bacterial substances

Area of Science:

• Immunology
• Nephrology
• Biomedical Engineering

Background:

• Inconsistent findings exist regarding the transfer of cytokine-inducing substances (CIS) across dialysis membranes.
• Differences in experimental design are suspected to cause these inconsistencies.

Purpose of the Study:

• To systematically evaluate cytokine induction in whole blood and peripheral blood mononuclear cells (PBMC) using lipopolysaccharide (LPS) and bacterial filtrates.
• To investigate the influence of hemodialysis circuit conditions and blood components on CIS detection.

Main Methods:

• An in vitro hemodialysis circuit model was used with whole blood and contaminated dialysate.
• Cytokine (IL-1beta, IL-6) induction was measured in whole blood and PBMC exposed to purified LPS or bacterial culture supernatants.
• The effect of erythrocytes, granulocytes, and plasma on cytokine induction was assessed.

Main Results:

• Plasma samples from the blood side induced IL-1beta and IL-6 in PBMC after dialysate contamination, but not in whole blood.
• Purified P. aeruginosa LPS induced more cytokines in whole blood than PBMC, while bacterial filtrates induced fewer cytokines in whole blood.
• Erythrocytes reduced cytokine induction by both LPS and bacterial filtrates, likely via adsorption.
• Plasma addition enhanced LPS-induced cytokine production but decreased it for P. aeruginosa filtrates.

Conclusions:

• Cellular and plasmatic components in whole blood interact with bacterial CIS, altering their pyrogenic activity.
• The sensitivity of CIS detection varies significantly with the test system; PBMC cultures are more sensitive than whole blood cultures for detecting CIS from bacterial filtrates.