Abstract
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.
Highlights
The ability to generate and respond to signaling molecules establishes a mechanism for regulated cell-to-cell communication
The findings from our studies described above [15,16,22] suggested that final outcome in patients with acute respiratory distress syndrome (ARDS) is related to the magnitude and duration of the host inflammatory response, and that intercurrent nosocomial infections (NIs) might be an epiphenomenon of prolonged intense inflammation
We found that exposure of LPS-primed U937 monocytic cells to methylprednisolone prior to infection affected the mRNA expression of tumor necrosis factor (TNF)-α, IL-1β, and IL-6, and the in vitro intracellular bacterial growth of internalized S. aureus, Ps. aeruginosa, and Acinetobacter sps [41]
Summary
The bidirectional effects of proinflammatory cytokines on bacterial growth may help explain the frequent occurrence of NIs in patients with unresolving ARDS. If NIs in unresolving ARDS are an epiphenomenon of exaggerated inflammation, it follows that treatment modalities that effectively decrease cytokine synthesis may reduce the incidence or severity of NIs
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