Dexamethasone Downregulates the Systemic Cytokine Response in Patients with Community-Acquired Pneumonia

Abstract

hThe 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-␣), gamma interferon (IFN-␥), macrophage inflammatory protein-1 alpha (MIP-1␣), 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-␣ (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-␣ (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.

Interleukin-17A in <i>Legionella</i> pneumonia: A Retrospective Study

“…In addition, IL-17A was detected in BAL fluids from Legionella pneumonia patients. The present findings suggest a clinical role for IL-17A in Legionella pneumonia, similar to the role reported in CAP associated with other bacterial pathogens (7)(8)(9). In addition, we demonstrated that the serum IL-17A levels did not correlate with the serum IFN-g or BAL fluid IL-17 levels in patients with Legionella pneumonia.…”

“…Recently, several groups examined the clinical roles of IL-17 in patients with community-acquired pneumonia (CAP) (7-9). Remmelts et al reported low systemic concentrations of IL-17 in CAP cases (7). Paats et al demonstrated that IL-17A was not detectable in the bronchoalveolar lavage (BAL) fluid and sera from patients with CAP (8), whereas such patients exhibited increased numbers of Th17 cells in the peripheral blood and bronchoalveolar (BA) space of patients with CAP (9).…”

Increased production of interleukin-10 in children with Down syndrome upon ex vivo stimulation with Streptococcus pneumoniae

“…In our study, IL-10 levels increased significantly from 6 to 48 h in the DS group in comparison to the controls. In adults with pneumococcal pneumonia, high levels of IL-10 were present in serum at admission and declined within 48 h while treated with antibiotics (34). In another study in humans with pneumococcal pneumoniae, high levels of IL-10 increased the in-hospital mortality rate (35).…”

Efeito da dexametasona e melatonina exógenas sobre parâmetros sanguíneos, progesterona, carboidratos totais e histomorfometria de órgãos em ratas prenhes

“…Alguns órgãos, como o pâncreas, o fígado e os rins, podem apresentar alterações morfofuncionais atribuídas à corticoterapia (Bruder et al, 2006). A dexametasona ainda exerce influência sobre a distribuição de células sanguíneas através da inibição da expressão de citocinas (Remmelts et al, 2012), redução drástica do número de linfócitos T, elevação acentuada de neutrófilos, além de uma redução acentuada dos linfócitos B, células NK (natural killer) e monócitos (Dhabhar et al, 1996).…”