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Dissociation between systemic and pulmonary anti ‐ inflammatory effects of dexamethasone in humans

View Article: PubMed Central - PubMed

ABSTRACT

Aims: The local pulmonary inflammatory response has a different temporal and qualitative profile compared with the systemic inflammatory response. Although glucocorticoids substantially downregulate the systemic release of acute‐phase mediators, it is not clear whether they have comparable inhibitory effects in the human lung compartment. Therefore, we compared the anti‐inflammatory effects of a pure glucocorticoid agonist, dexamethasone, on bronchoalveolar lavage and blood cytokine concentrations in response to bronchially instilled endotoxin.

Methods: In this randomized, double‐blind and placebo‐controlled trial, 24 volunteers received dexamethasone or placebo and had endotoxin instilled into a lung segment and saline instilled into a contralateral segment, followed by bronchoalveolar lavage.

Results: Bronchially instilled endotoxin induced a local and systemic inflammatory response. Dexamethasone strongly blunted the systemic interleukin (IL) 6 and C‐reactive protein release. In sharp contrast, dexamethasone left the local release of acute‐phase mediators in the lungs virtually unchanged: bronchoalveolar lavage levels of IL‐6 were only 18% lower and levels of IL‐8 were even higher with dexamethasone compared with placebo, although the differences between treatments were not statistically significant (P = 0.07 and P = 0.08, respectively). However, dexamethasone had inhibitory effects on pulmonary protein extravasation and neutrophil migration.

Conclusions: The present study demonstrated a remarkable dissociation between the systemic anti‐inflammatory effects of glucocorticoids and its protective effects on capillary leak on the one hand and surprisingly low anti‐inflammatory effects in the lungs on the other.

No MeSH data available.


Related in: MedlinePlus

Consolidated Standards of Reporting Trials flow diagram. Twenty‐eight subjects were screened, and three were excluded (two had a cough and fever a week before the first trial day, and one individual declined to participate). In one subject allocated to the placebo group, no endotoxin or saline was instilled because obstructive sleep apnoea was suspected when sedation was initialized
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bcp12857-fig-0002: Consolidated Standards of Reporting Trials flow diagram. Twenty‐eight subjects were screened, and three were excluded (two had a cough and fever a week before the first trial day, and one individual declined to participate). In one subject allocated to the placebo group, no endotoxin or saline was instilled because obstructive sleep apnoea was suspected when sedation was initialized

Mentions: From a total of 28 screened volunteers, three subjects were excluded. Two individuals had symptoms of a clinically relevant illness (cough and fever) a week before the first trial day, and one individual declined to participate. In one subject allocated to placebo, no endotoxin or saline was instilled because obstructive sleep apnoea was suspected when sedation was initialized and the subject was therefore excluded from analysis (Figure 2). Trial participants had comparable baseline characteristics (Table 1). The endotoxin challenge was well tolerated among all subjects and no severe adverse events occurred. Two subjects had a mild cough and one subject developed chills and fever transiently. Symptoms associated with the BAL procedure included fever (four subjects, all allocated to placebo; mean fever onset after BAL: 4.5 h), cough (eight subjects), throat pain (three subjects) and vomiting (two subjects). There was a small, but significant increase in body temperature, from a median of 35.9 °C to 36.3 °C (P = 0.012 at 7–9 h), which was slightly more pronounced among placebo‐treated individuals (median increase: placebo 0.45 °C vs. dexamethasone 0.30 °C).


Dissociation between systemic and pulmonary anti ‐ inflammatory effects of dexamethasone in humans
Consolidated Standards of Reporting Trials flow diagram. Twenty‐eight subjects were screened, and three were excluded (two had a cough and fever a week before the first trial day, and one individual declined to participate). In one subject allocated to the placebo group, no endotoxin or saline was instilled because obstructive sleep apnoea was suspected when sedation was initialized
© Copyright Policy - creativeCommonsBy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834593&req=5

bcp12857-fig-0002: Consolidated Standards of Reporting Trials flow diagram. Twenty‐eight subjects were screened, and three were excluded (two had a cough and fever a week before the first trial day, and one individual declined to participate). In one subject allocated to the placebo group, no endotoxin or saline was instilled because obstructive sleep apnoea was suspected when sedation was initialized
Mentions: From a total of 28 screened volunteers, three subjects were excluded. Two individuals had symptoms of a clinically relevant illness (cough and fever) a week before the first trial day, and one individual declined to participate. In one subject allocated to placebo, no endotoxin or saline was instilled because obstructive sleep apnoea was suspected when sedation was initialized and the subject was therefore excluded from analysis (Figure 2). Trial participants had comparable baseline characteristics (Table 1). The endotoxin challenge was well tolerated among all subjects and no severe adverse events occurred. Two subjects had a mild cough and one subject developed chills and fever transiently. Symptoms associated with the BAL procedure included fever (four subjects, all allocated to placebo; mean fever onset after BAL: 4.5 h), cough (eight subjects), throat pain (three subjects) and vomiting (two subjects). There was a small, but significant increase in body temperature, from a median of 35.9 °C to 36.3 °C (P = 0.012 at 7–9 h), which was slightly more pronounced among placebo‐treated individuals (median increase: placebo 0.45 °C vs. dexamethasone 0.30 °C).

View Article: PubMed Central - PubMed

ABSTRACT

Aims: The local pulmonary inflammatory response has a different temporal and qualitative profile compared with the systemic inflammatory response. Although glucocorticoids substantially downregulate the systemic release of acute‐phase mediators, it is not clear whether they have comparable inhibitory effects in the human lung compartment. Therefore, we compared the anti‐inflammatory effects of a pure glucocorticoid agonist, dexamethasone, on bronchoalveolar lavage and blood cytokine concentrations in response to bronchially instilled endotoxin.

Methods: In this randomized, double‐blind and placebo‐controlled trial, 24 volunteers received dexamethasone or placebo and had endotoxin instilled into a lung segment and saline instilled into a contralateral segment, followed by bronchoalveolar lavage.

Results: Bronchially instilled endotoxin induced a local and systemic inflammatory response. Dexamethasone strongly blunted the systemic interleukin (IL) 6 and C‐reactive protein release. In sharp contrast, dexamethasone left the local release of acute‐phase mediators in the lungs virtually unchanged: bronchoalveolar lavage levels of IL‐6 were only 18% lower and levels of IL‐8 were even higher with dexamethasone compared with placebo, although the differences between treatments were not statistically significant (P = 0.07 and P = 0.08, respectively). However, dexamethasone had inhibitory effects on pulmonary protein extravasation and neutrophil migration.

Conclusions: The present study demonstrated a remarkable dissociation between the systemic anti‐inflammatory effects of glucocorticoids and its protective effects on capillary leak on the one hand and surprisingly low anti‐inflammatory effects in the lungs on the other.

No MeSH data available.


Related in: MedlinePlus