Impact of minocycline on cerebrospinal fluid markers of oxidative stress, neuronal injury, and inflammation in HIV-seropositive individuals with cognitive impairment.
Elevated cerebrospinal fluid (CSF) levels of markers of oxidative stress, neuronal injury, and inflammation and decreased neurotransmitter levels have been reported in HIV-associated neurocognitive disorders (HAND). Minocycline may have a neuroprotective effect by inhibiting inducible nitric oxide synthase, which produces nitric oxide, a compound that induces oxygen free radical production. In A5235, "Phase II, Randomized, Placebo-Controlled, Double-Blind Study of Minocycline in the Treatment of HIV-Associated Cognitive Impairment," minocycline was not associated with cognitive improvement, but the effect on the above CSF measures was not examined previously. The objective of this study was to examine the effect of minocycline on markers of oxidative stress, neuronal injury, neurotransmitter levels, and inflammation from CSF in participants in A5235. One hundred seven HIV+ individuals received either minocycline 100 mg or placebo orally every 12 h for 24 weeks. Twenty-one HIV+ individuals received the optional lumbar punctures. Lipid and protein markers of oxidative stress (e.g., ceramides and protein carbonyls), glutamate, neurotransmitter precursors, kynurenine metabolites, neurofilament heavy chain, and inflammatory cytokines were measured in the CSF before and after treatment. The 24-week change in ceramides was larger in a beneficial direction in the minocycline group compared to the placebo group. The two groups did not differ in the 24-week changes for other markers.These results suggest that minocycline may decrease lipid markers of oxidative stress (ceramides) in individuals with HAND; however, an effect of minocycline on other CSF markers was not observed. A larger sample size is needed to further validate these results.
Johns Hopkins University School of Medicine, Baltimore, MD, USA, sacktor@jhmi.edu.
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Sacktor
Sachiko
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Miyahara
Scott
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Evans
Giovanni
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Schifitto
Bruce
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Cohen
Norman
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Haughey
Julia L
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Drewes
David
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Graham
M Christine
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Zink
Caroline
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Anderson
Avindra
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Nath
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Pardo
Sean
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McCarthy
Lara
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Hosey
David
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Clifford
D015526:AIDS Dementia Complex / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D000163:Acquired Immunodeficiency Syndrome / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D000284:Administration, Oral; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D002518:Ceramides / Q000134:cerebrospinal fluid; D016207:Cytokines / Q000134:cerebrospinal fluid; D004311:Double-Blind Method; D005260:Female; D018698:Glutamic Acid / Q000134:cerebrospinal fluid; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007737:Kynurenine / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000627:therapeutic use*; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000821:virology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D052247:Nitric Oxide Synthase Type II / Q000134:cerebrospinal fluid; D018384:Oxidative Stress
D019380:Anti-HIV Agents; D002518:Ceramides; D016207:Cytokines; D016900:Neurofilament Proteins; D018696:Neuroprotective Agents; C051774:neurofilament protein H; D007737:Kynurenine; D018698:Glutamic Acid; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D008911:Minocycline