Interleukin-1 beta and tumor necrosis factor-alpha are expressed by different subsets of microglia and macrophages after ischemic stroke in mice

Background: Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are expressed by microglia and infiltrating macrophages following ischemic stroke. Whereas IL-1 beta is primarily neurotoxic in ischemic stroke, TNF-alpha may have neurotoxic and/or neuroprotective effects. We investigated whether IL-1 beta and TNF-alpha are synthesized by overlapping or segregated populations of cells after ischemic stroke in mice. Methods: We used flow cytometry and immunohistochemistry to examine cellular co-expression of IL-1 beta and TNF-alpha at 6, 12 and 24 hours after permanent middle cerebral artery occlusion in mice, validating the results by the use of bone marrow chimeric mice. Results: We found that IL-1 beta and TNF-alpha were expressed in largely segregated populations of CD11b(+)CD45(dim) microglia and CD11b(+)CD45(high) macrophages, with cells expressing both cytokines only rarely. The number of Gr1(+) granulocytes producing IL-1 beta or TNF-alpha was very low, and we observed no IL-1 beta- or TNF-alpha-expressing T cells or astrocytes. Conclusion: Taken together, the results show that IL-1 beta and TNF-alpha are produced by largely segregated populations of microglia and macrophages after ischemic stroke in mice. Our findings provide evidence of a functional diversity among different subsets of microglia and macrophages that is potentially relevant to future design of anti-inflammatory therapies in stroke.