Dexamethasone downregulates the systemic cytokine response in patients with community-acquired pneumonia

Abstract

The influence of adjunctive corticosteroids on the cytokine response in community-acquired pneumonia (CAP) is largely unknown. In this study, we analyzed the effect of dexamethasone on the cytokine response in patients with CAP and evaluated whether this effect is dependent on the causative microorganism. We hypothesized that dexamethasone has a larger effect on the cytokine response in patients with pneumococcal pneumonia than in patients with pneumonia caused by an atypical bacterium. A total of 304 hospitalized, nonimmunocompromised patients with CAP were randomized to an adjunctive 4-day course of 5 mg dexamethasone once a day (n = 151) or a placebo (n = 153). Serum concentrations of interleukin-1 receptor antagonist (IL-1Ra), IL-6, IL-8, IL-10, IL-17, tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), macrophage inflammatory protein-1 alpha (MIP-1α), and monocyte chemotactic protein-1 (MCP-1) were measured on days 0, 1, 2, and 4 and at a control visit. Overall, the concentrations of IL-6 (P < 0.01), IL-8 (P < 0.01), MCP-1 (P < 0.01), and TNF-α (P < 0.01) were significantly lower on day 2 in the dexamethasone group than in the placebo group. In patients with pneumococcal pneumonia (n = 72), both treatment groups showed a rapid decrease of cytokine concentrations; only the concentration of TNF-α (P = 0.05) was significantly lower in the dexamethasone group on day 2. In patients with CAP caused by an atypical pathogen (Legionella pneumophila, Chlamydophila species, Coxiella burnetii, or Mycoplasma pneumoniae; n = 58), IL-1Ra (P < 0.01), IL-6 (P < 0.01), and MCP-1 (P = 0.03) decreased more rapidly in the dexamethasone group than in the placebo group. In conclusion, dexamethasone downregulates the cytokine response during CAP. This effect seems to be dependent on the causative microorganism. This study provides insight into which patients with CAP might benefit most from adjunctive dexamethasone.

Fig 1

Median serum cytokine concentrations (with interquartile ranges) in patients with community-acquired pneumonia treated with either dexamethasone or placebo, from hospital admission to day 30. The asterisks indicate significant differences in the cytokine concentrations on day 2 between the placebo and dexamethasone groups (corrected for the magnitude of the cytokine response on day 0).

Fig 2

Influence of dexamethasone on median serum cytokine concentrations (with interquartile ranges) in patients with community-acquired pneumonia caused by either Streptococcus pneumoniae or an atypical bacterium, from hospital admission to day 30. This figure represents those cytokines that showed significantly different patterns in the two treatment groups, as indicated by an asterisk. Atypical bacteria include L. pneumophila, M. pneumoniae, Chlamydophila species, and C. burnetii.

Fig 3

Influence of dexamethasone on median serum cytokine concentrations (with interquartile ranges) in patients with community-acquired pneumonia caused by either Streptococcus pneumoniae or an atypical bacterium, from hospital admission to day 30. This figure represents the cytokines that did not show different patterns in the two treatment groups. Atypical bacteria include L. pneumophila, M. pneumoniae, Chlamydophila species, and C. burnetii. The concentrations of IL-17 and MIP-1α in most cases fell out of range, below 3.2 pg/ml, which precluded reporting of the courses of these cytokines for the separate etiological groups.