The effect of Pseudomonas exotoxin A on cytokine production in whole bloodexposed to Pseudomonas aeruginosa

To determine the effect of Pseudomonas aeruginosa exotoxin A (P-ExA) on cyt okine production, we studied cytokine release induced by heat-killed P. aer uginosa (HKPA) in human whole blood in the presence or absence of P-ExA. P- ExA (0.01-1 mug ml(-1)) caused a dose-dependent decrease in HKPA-induced pr oduction of tumor necrosis factor alpha (TNF), interleukin (IL-) 10, IL-6 a nd IL-8 (ail P < 0.05). P-ExA-induced inhibition of IL 10, IL-6 and IL-8 re lease was not dependent on reduced TNF concentrations, since the relative a ttenuation of the production of those cytokines was similar in the presence or absence of a neutralizing anti-TNF antibody. The effect of P-ExA on cyt okine production may offer a disadvantage to the host with respect to clear ance of the infection. (C) 2000 Federation of European Microbiological Soci eties. Published by Elsevier Science B.V. All rights reserved.