The Interleukin-8 (IL-8/CXCL8) Receptor Inhibitor Reparixin Improves Neurological Deficits and Reduces Long-term Inflammation in Permanent and Transient Cerebral Ischemia in Rats

Pia Villa, Sara Triulzi, Barbara Cavalieri,  Rosa Di Bitondo, Riccardo Bertini, Sara Barbera, Paolo Bigini, Tiziana Mennini, Paolo Gelosa, Elena Tremoli, Luigi Sironi, and Pietro Ghezzi

Infiltration of neutrophils, or polymorphonuclear leukocytes (PMNs), contributes to the deleterious aspects of inflammation during stroke.  Interleukin-8 (IL-8/CXCL8), in conjunction with other chemokines, is induced during stroke in patients and animals models of cerebral ischemia. Blocking inflammation by inhibiting these mediators is a plausible therapy for cerebral ischemia.  Reparixin is an inhibitor of CXCR1 and CXCR2, the receptors for the CXCL8 family of chemokines implicated in the recruitment of PMNs. In this study, Villa et al. (125-133) evaluated the effects of reparixin in two cerebral ischemia models, transient and permanent middle cerebral artery occlusion, using varied treatment schedules and therapeutic windows.  Data indicate that reparixin not only reduces short-term PMN infiltration and infarct size, but also decreases long-term inflammation and improves long-term neurological outcome in transient and permanent ischemia models.  These results support the notion that CXCL8-mediated inflammation plays an important role in ischemic damage and CXCR1/2 inhibitors may represent a therapeutic strategy for the treatment of cerebral ischemia.

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Posted by Leah Caracappa on Apr 3, 2012 8:16 AM CDT