Experimental stroke induces massive, rapid activation of the peripheral immune system.
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-alpha, IFN-gamma, IL-6, MCP-1, and IL-2. Unstimulated splenocytes expressed increased chemokines and CCR, including MIP-2 and CCR2, CCR7 and CCR8 at 6 h; and MIP-2, IP-10, and CCR1 and 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.
Offner
Halina
H
Neuroimmunology Research, Veterans Affairs Medical Center, Portland, Oregon 97239, USA. offnerva@ohsu.edu
Subramanian
Sandhya
S
Parker
Susan M
SM
Afentoulis
Michael E
ME
Vandenbark
Arthur A
AA
Hurn
Patricia D
PD
D000818:Animals; D001769:Blood / Q000276:immunology; D001921:Brain / Q000166:cytology / Q000276:immunology; D018925:Chemokines / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D007107:Immune System / Q000502:physiology*; D020244:Infarction, Middle Cerebral Artery; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology*; D013116:Spinal Cord / Q000166:cytology / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D020521:Stroke / Q000276:immunology*
D018925:Chemokines; D016207:Cytokines; D019707:Receptors, Chemokine