Interferon-beta fails to protect in a model of transient focal stroke.
OBJECTIVE
Compelling evidence supporting the role of inflammation in the development of cerebral infarction has focused attention on the potential of antiinflammatory treatment strategies for stroke. Interferon (IFN)-beta, an immunomodulatory agent approved for treatment of multiple sclerosis, is being evaluated in a phase I clinical trial in acute ischemic stroke. In the present study, we evaluated the effects of wild-type rat IFN-beta and its pegylated counterpart (PEG-IFN-beta) in a model of focal ischemia and reperfusion.


METHODS
After 60 minutes of middle cerebral artery occlusion, rats (n=12/group) were treated with IV tail injections of 8 or 16 mug of IFN-beta in 300 muL of PBS once daily for 3 or 7 days or with IV or SC injections of PEG-IFN-beta for 1 day. The animals were assessed daily for weight and for neurological findings. Additional animals underwent complete hematology and chemistry profiles, as well as complete multiorgan necropsy studies. All of the brain tissue was evaluated for assessment of infarct areas, neutrophil infiltration, and presence of hemorrhagic transformations.


RESULTS
IFN-beta and PEG-IFN-beta failed to protect against experimental ischemic brain injury as assessed by histopathology and neurological outcome. Furthermore, IFN-beta treatment was associated with significant weight loss and alterations in hematology and chemistry profiles.


CONCLUSIONS
Our results suggest that additional preclinical studies are warranted.
Maier
Carolina M
CM
Department of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA.
Yu
Fengshan
F
Nishi
Tatsuro
T
Lathrop
Stephanie J
SJ
Chan
Pak H
PH
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D007155:Immunologic Factors / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D002546:Ischemic Attack, Transient / Q000150:complications*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology; D020521:Stroke / Q000097:blood / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*
D007155:Immunologic Factors; D018696:Neuroprotective Agents; D011092:Polyethylene Glycols; D016899:Interferon-beta