Clinical review: a paradigm shift: the bidirectional effect of inflammation on bacterial growth. Clinical implications for patients with acute respiratory distress syndrome.

Clinical studies have shown positive associations among sustained and intense inflammatory responses and the incidence of bacterial infections. We hypothesized that cytokines secreted by the host during acute respiratory distress syndrome may indeed favor the growth of bacteria and explain the association between exaggerated and protracted systemic inflammation and the frequent development of nosocomial infections. To test this hypothesis, we conducted in vitro studies evaluating the extracellular and intracellular growth response of three clinically relevant bacteria in response to graded concentrations of pro-inflammatory cytokines tumor necrosis factor-alpha, IL-1beta, and IL-6. In these studies, we identified a U-shaped response of bacterial growth to pro-inflammatory cytokines. When the bacteria were exposed in vitro to a lower concentration of cytokines, extracellular and intracellular bacterial growth was not promoted and human monocytic cells were efficient in killing the ingested bacteria. Conversely, when bacteria were exposed to higher concentrations of pro-inflammatory cytokines, intracellular and extracellular bacterial growth was enhanced in a dose-dependent manner. The bidirectional effects of proinflammatory cytokines on bacterial growth may help to explain the frequent occurrence of nosocomial infections in patients with unresolving acute respiratory distress syndrome.