NEW YORK (Reuters Health) - Studies in an animal model of HIV infection suggest that minocycline may reduce the incidence and severity of encephalitis due to the virus, investigators report in the Journal of the American Medical Association for April 27.
Antiretroviral drugs fail to adequately protect the central nervous system in HIV, Dr. M Christine Zink and colleagues explain. Minocycline, on the other hand, is neuroprotective in animal models of ALS, multiple sclerosis and other brain disorders, has potent anti-inflammatory properties, and effectively crosses the blood-brain barrier.
To study the drug’s ability to protect against encephalitis and neurodegeneration, Dr. Zink, at Johns Hopkins University School of Medicine in Baltimore, and colleagues infected pigtailed macaques with simian immunodeficiency virus (SIV), an animal model of HIV. Starting 21 days later, five macaques were treated with minocycline 4 mg/kg/day, while six animals remained untreated.
At day 84 -- a time that corresponds to late-stage infection in HIV-infected patients -- minocycline had significantly reduced the incidence and severity of encephalitis (p = 0.02).
Analysis of cerebrospinal fluid showed that minocycline treatment led to significantly reduced levels of major histocompatibility complex class II antigens, “indicating suppressed activation of macrophages, endothelial cells, or both in the brain,” the authors note.
Reductions in other neuroinflammatory markers signified decreased infiltration and activation of macrophages and cytotoxic lymphocytes. A marker of axonal degeneration (beta-amyloid precursor protein) was also significantly decreased, as were levels of proinflammatory chemokines.
Moreover, minocycline also suppressed SIV replication in cerebrospinal fluid and brain tissue.
In vitro studies showed that the antibiotic inhibited HIV and SIV replication in cultured macrophages and lymphocytes.
Dr. Zink’s group proposes that “rather than exerting direct antiviral activity, minocycline modifies the intracellular or extracellular environment making it nonpermissive for HIV or SIV replication.”
They therefore recommend trials “to examine the potential role of minocycline as a supplement to highly active antiretroviral therapy in the treatment of HIV-associated cognitive disorders and in maintaining low viral loads in patients for whom highly active antiretroviral therapy must be discontinued.”
Source: JAMA 2005;293:2003-2011. [ Google search on this article ]
MeSH Headings:Biological Factors: Chemotactic Factors: Cytotoxicity, Immunologic: Immunity, Cellular: Immunologic and Biological Factors: Immunologic Techniques: Lymphocyte Transformation: Macrophage Activation: Investigative Techniques: Chemokines: Chemical Actions and Uses: Chemical Actions: Analytical, Diagnostic and Therapeutic Techniques and Equipment: Chemicals and DrugsCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
