Brain Extracellular Interleukin-6 Levels Decrease Following Antipyretic Therapy with Diclofenac in Patients with...

Area of Science:

• Neuroscience
• Pharmacology
• Critical Care Medicine

Background:

• Elevated brain extracellular interleukin-6 (IL-6) in aneurysmal subarachnoid hemorrhage (aSAH) correlates with poor outcomes.
• Interleukin-6 is a key pro-inflammatory cytokine implicated in early brain injury and delayed cerebral infarction.

Purpose of the Study:

• To investigate the effect of parenteral diclofenac on brain extracellular IL-6 levels in mechanically ventilated poor-grade aSAH patients.
• To assess whether diclofenac administration influences inflammatory markers in the context of aSAH.

Main Methods:

• Retrospective analysis of prospectively collected bedside data from 24 mechanically ventilated aSAH patients.
• Cerebral microdialysis (CMD) was used to measure brain extracellular IL-6 levels before and at 2, 4, and 8 hours after intravenous diclofenac infusion (DCF).
• Statistical analysis employed generalized estimating equations to evaluate changes in IL-6 levels.

Main Results:

• Baseline CMD-IL-6 levels were significantly higher in patients with fever, higher modified Fisher grades, delayed cerebral infarction, and metabolic distress.
• Parenteral diclofenac administration led to a significant decrease in brain extracellular IL-6 levels at 2, 4, and 8 hours post-infusion (p < 0.001).
• The reduction in IL-6 was observed independent of probe location or the day after the initial bleeding event.

Conclusions:

• Parenteral diclofenac demonstrated a potent ability to attenuate the brain's extracellular pro-inflammatory response in poor-grade aSAH patients.
• These findings suggest a potential therapeutic role for diclofenac in mitigating inflammatory processes following aneurysmal subarachnoid hemorrhage.
• Further research is warranted to confirm the clinical efficacy of diclofenac in improving outcomes for aSAH patients.