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Minocycline Prevents IL-6 Increase after Acute Ischemic Stroke

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Abstract

Higher levels of the inflammatory biomarker interleukin-6 (IL-6) correlate with poor clinical outcome in acute ischemic stroke (AIS). Minocycline (MC) is a known anti-inflammatory agent; thus, the effect of MC on IL-6 in the first 24 h of AIS was investigated to determine potential anti-inflammatory activity. The Minocycline to Improve Neurologic Outcome in Stroke (MINOS) study was a non-randomized dose-escalation (3.0–10.0 mg/kg) trial of IV MC for AIS within 6 h of onset. Plasma IL-6 samples were collected prior to MC treatment at 1, 24, and 72 h and compared to those collected in a separate observational study of blood biomarkers in AIS. IL-6 levels were measured by commercially available ELISA kits. The lower limit of detection for IL-6 was 1 pg/ml. Sixty MINOS subjects and 29 non-MINOS subjects were enrolled, and there was no difference in baseline stroke severity. There was no significant difference in IL-6 level pre-MC treatment at 1, 24, or 72 h. However, the odds of a non-detectable IL-6 at 24 h in MINOS were 8.94 (95% CI 2.62–30.46) compared with non-MINOS subjects. It is likely that even low doses of MC have a potent systemic anti-inflammatory effect in AIS. Whether this results in improved outcome will be tested in a randomized clinical trial.

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Acknowledgments

This study was supported by the NIH/NINDS grants (DCH, R01 NS055728; SCF, RO1 NS063965; and AE, R21 NS070239), AHA EIA (AE, 0740002N), and the MCG Intramural Grants Program Scientist Training Program to JAS.

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Authors and Affiliations

  1. Department of Neurology, Georgia Health Sciences University, 1120 15th St, Augusta, GA, 30912, USA

    Jeffrey A. Switzer, David C. Hess & Susan C. Fagan

  2. Department of Physiology, Georgia Health Sciences University, Augusta, GA, 30912, USA

    Adviye Ergul

  3. Department of Biostatistics, Georgia Health Sciences University, Augusta, GA, 30912, USA

    Adviye Ergul & Jennifer L. Waller

  4. Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA, 30912, USA

    Andrea Sikora, Adviye Ergul, David C. Hess & Susan C. Fagan

  5. Charlie Norwood VA Medical Center, Augusta, GA, 30912, USA

    Adviye Ergul & Susan C. Fagan

Authors
  1. Jeffrey A. Switzer
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  2. Andrea Sikora
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  3. Adviye Ergul
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  4. Jennifer L. Waller
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  5. David C. Hess
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  6. Susan C. Fagan
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Correspondence to Jeffrey A. Switzer.

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Switzer, J.A., Sikora, A., Ergul, A. et al. Minocycline Prevents IL-6 Increase after Acute Ischemic Stroke. Transl. Stroke Res. 3, 364–368 (2012). https://doi.org/10.1007/s12975-012-0150-4

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  • DOI: https://doi.org/10.1007/s12975-012-0150-4

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