1. ¹Neuroimmunology Research, Veterans Affairs Medical Center, Portland, Oregon, USA
2. ²Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon, USA
3. ³Department of Neurology, Oregon Health and Science University, Portland, Oregon, USA
4. ⁴Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon, USA

Correspondence: Professor H Offner, Neuroimmunology Research R&D-31, Portland VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, OR 97239, USA. E-mail: offnerva@ohsu.edu

Received 5 May 2005; Revised 20 June 2005; Accepted 14 July 2005; Published online 24 August 2005.

Abstract

Clinical experimental stroke induces injurious local brain inflammation. However, effects on the peripheral immune system have not been well characterized. We quantified mRNA and protein levels for cytokines, chemokines, and chemokine receptors (CCR) in brain, spinal cord, peripheral lymphoid organs (spleen, lymph node, blood, and cultured mononuclear cells from these sources), and blood plasma after reversible middle cerebral artery occlusion (MCAO) or sham treatment in male C57BL/6 mice. Middle cerebral artery occlusion induced a complex, but organ specific, pattern of inflammatory factors in the periphery. At both 6 and 22 h after MCAO, activated spleen cells from stroke-injured mice secreted significantly enhanced levels of TNF-, IFN-, IL-6, MCP-1, and IL-2. Unstimulated splenocytes expressed increased chemokines and CCR, including MIP-2 and CCR2, CCR7 & CCR8 at 6 h; and MIP-2, IP-10, and CCR1 & CCR2 at 22 h. Also at 22 h, T cells from blood and lymph nodes secreted increased levels of inflammatory cytokines after activation. As expected, there were striking proinflammatory changes in postischemic brain. In contrast, spinal cord displayed suppression of all mediators, suggesting a compensatory response to intracranial events. These data show for the first time that focal cerebral ischemia results in dynamic and widespread activation of inflammatory cytokines, chemokines, and CCR in the peripheral immune system.