Is minocycline useful for therapy of acute viral encephalitis?
Minocyline is a tetracycline derivative with anti-inflammatory, anti-apoptotic, and anti-oxidant properties. Therapy has proved useful in some experimental models of both noninfectious and infectious neurological diseases and also in clinical trials in humans, including acute traumatic cervical spinal cord injury. In models of viral encephalitis, treatment has shown both beneficial and deleterious effects. In reovirus infection in mice, minocycline delayed the disease, but did not improve either the morbidity or mortality of the disease. In neuroadapted Sindbis virus infection of mice, minocycline prevented disease, but therapy needed to be given before clinical signs were present in most of the animals. In experimental rabies in neonatal mice minocycline aggravated the disease, likely related to anti-inflammatory effects. Minocycline has also been shown to aggravate disease in a mouse model of Huntington disease, in a monkey model of Parkinson disease, and in a mouse model of hypoxic-ischemic brain injury. Hence, there is experimental evidence of benefit of minocycline in both infectious and noninfectious neurological diseases, but there is a lack of benefit and harmful effects in other diseases. This may reflect multiple mechanisms of actions that cannot be predicted in a new disease or in an infection caused by a specific viral agent. Minocycline therapy is a double-edged sword and this drug should not be given empirically to patients with acute viral encephalitis for anticipated neuroprotective effects. Much more work needs to be done in experimental models in animals as well as in clinical trials. Because patient enrollment in clinical trials on acute viral encephalitis has proven to be difficult, funding will be a challenge.
Departments of Internal Medicine (Neurology) and of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada. ajackson2@hsc.mb.ca
Alan C
AC
Jackson
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D064420:Drug-Related Side Effects and Adverse Reactions; D018792:Encephalitis, Viral / Q000188:drug therapy*; D004679:Encephalomyelitis / Q000188:drug therapy; D051379:Mice; D008911:Minocycline / Q000008:administration & dosage* / Q000009:adverse effects*; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D008911:Minocycline