Cytokines IL-1 beta, IL-6, and TNF-alpha enhance in vitro growth of bacteria

We have previously reported that in acute respiratory distress syndrome (AR DS), nonsurvivors have persistent elevation in pulmonary and circulating pr oinflammatory cytokine levels over time and a high rate of nosocomial infec tions antemortem. In these patients, none of the proven or suspected nosoco mial infections caused a transient or sustained increase in plasma proinfla mmatory cytokine levels above preinfection values. We hypothesized that cyt okines secreted by the host during ARDS may favor the growth of bacteria. W e conducted an in vitro study of the growth of three bacteria clinically re levant in nosocomial infections, evaluating their in vitro response to vari ous concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-6. We found that all three bacterial species showed concentra tion-dependent growth enhancement when incubated with one or more tested cy tokines and that blockade by specific neutralizing cytokine MoAb significan tly inhibited cytokine-induced growth. When compared with control, the 6-h growth response (cfu/ml) was maximal with II-1 beta at 1,000 pg for Staphyl ococcus aureus (36 +/- 16 versus 377 +/- 16; p = 0.0001) and Acinetobacter spp. (317 +/- 1,147 versus 1,124 +/- 147; p = 0.002) and with IL-6 at 1,000 pg for Pseudomonas aeruginosa (99 +/- 50 versus 509 +/- 50; p = 0.009). Th e effects of cytokines were seen only with fresh isolates and were lost wit h passage in vitro on bacteriologic medium without added cytokines. In this study we provide additional evidence for a newly described pathogenetic me chanism for bacterial proliferation in the presence of exaggerated and prot racted inflammation.