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High-dose dexamethasone induced LPS-stimulated rat alveolar macrophages apoptosis
Si Zeng1, Hui Qiao2, Xue-Wen Lv1
1Department of Anesthesiology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu.
Abstract:
Prolonged administration of an excessive dose of corticosteroids proved to be harmful for patients with acute lung injury (ALI). A previous study has found that repeated administration of an excessive dose of methylprednisolone reduced alveolar macrophages (AMs) in bronchoalveolar lavage fluid (BALF) with an unknown mechanism. This study aimed to investigate the effect of excessive use of dexamethasone (Dex) on BALF AMs in vitro. Transmission electron microscopy and DNA fragmentation analysis demonstrated that 10-4 and 10-5 M Dex induced lipopolysaccharide-stimulated rat AMs apoptosis with downregulation of tumor necrosis factor-α, interleukin (IL)-12 and upregulation of IL-10, transforming growth factor-β. These results indicated that apoptosis might be a novel contribution involved in the detrimental effect of excessive dose of Dex clinically used to treat ALI.
Insights
Excessive corticosteroid use in acute lung injury (ALI) harms patients. This study shows high-dose dexamethasone induces apoptosis in rat alveolar macrophages (AMs), potentially explaining clinical harm.
Area of Science:
- Pulmonology
- Immunology
- Pharmacology
Background:
- Prolonged, excessive corticosteroid doses are detrimental in acute lung injury (ALI).
- Previous research indicated methylprednisolone reduced alveolar macrophages (AMs) in bronchoalveolar lavage fluid (BALF) via unknown mechanisms.
- Understanding the impact of excessive corticosteroids on AMs is crucial for ALI treatment.
Purpose of the Study:
- To investigate the in vitro effects of excessive dexamethasone (Dex) on rat AMs from BALF.
- To elucidate the cellular mechanisms underlying the detrimental effects of high-dose Dex in ALI.
Main Methods:
- Primary rat AMs were isolated and stimulated with lipopolysaccharide.
- Cells were treated with varying concentrations of dexamethasone (10-4 M and 10-5 M).
- Apoptosis was assessed using transmission electron microscopy and DNA fragmentation analysis. Cytokine profiles were analyzed.
Main Results:
- Dexamethasone at 10-4 M and 10-5 M induced significant apoptosis in LPS-stimulated rat AMs.
- This apoptosis was associated with the downregulation of pro-inflammatory cytokines tumor necrosis factor-α and IL-12.
- Concurrently, anti-inflammatory cytokines IL-10 and transforming growth factor-β were upregulated.
Conclusions:
- Excessive dexamethasone administration induces apoptosis in AMs.
- AM apoptosis may be a key mechanism contributing to the harmful clinical effects of high-dose Dex in ALI.
- These findings suggest a novel pathway for corticosteroid-induced toxicity in ALI.
