Allometric Dose Retranslation Unveiled Substantial Immunological Side Effects of Granulocyte Colony–Stimulating Factor After Stroke by Daniel-Christoph.

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Allometric Dose Retranslation Unveiled Substantial Immunological Side Effects of Granulocyte Colony–Stimulating Factor After Stroke by Daniel-Christoph Wagner, Claudia Pösel, Isabell Schulz, Gerda Schicht, Johannes Boltze, Franziska Lange, Johanna Scheibe, Karoline Möller, and Gesa Weise Stroke Volume 45(2):623-626 January 27, 2014 Copyright © American Heart Association, Inc. All rights reserved.

Impact of granulocyte colony–stimulating factor (GCSF) on neurological deficit, infarct volume, and peripheral leukocyte distribution 24 hours after middle cerebral artery occlusion (MCAO). Impact of granulocyte colony–stimulating factor (GCSF) on neurological deficit, infarct volume, and peripheral leukocyte distribution 24 hours after middle cerebral artery occlusion (MCAO). A, Bederson score (percentage distribution, animal numbers are indicated in columns) and edema-corrected hemispheric lesion volume (%HLVe). *P<0.05. B, Natural killer (NK) cells, mononuclear (mn) myeloid cells, granulocytes (polymorphonuclear cells [PMN]), B cells, cytotoxic T cells (CD8+), and T-helper cells (Th, CD4+) were assessed in blood and spleen. *P<0.05 naive vs sham/MCAO/GCSF low/high; †P<0.05 naive vs GCSF low/high; ‡P<0.05 naive vs GCSF high. C, Th-cell subpopulations in spleen and blood. D, Serum cytokines. **P<0.01, ***P<0.001 (n=3–8). HD indicates high dose; IL, interleukin; and LD, low dose. Daniel-Christoph Wagner et al. Stroke. 2014;45:623-626 Copyright © American Heart Association, Inc. All rights reserved.

Differentiation of circulating myeloid subpopulations. Differentiation of circulating myeloid subpopulations. A, Nongranulocyte CD11b+ cells were distinguished by CD11c/major histocompatibility complex (MHC) II/Ly6C. Q1, CD11c+/MHCII–/Ly6C+ and – cells significantly increased after granulocyte colony–stimulating factor (GCSF) high treatment. Histogram, note the shift toward Ly6C+ in GCSF high group. CD11c+/MHCII+ (Q2), CD11c–/MHCII+ (Q3), and CD11c–/MHCII– (Q4) did not differ among groups. B, Lymphoid dendritic cell counts in blood and spleen. *P<0.05, **P<0.01, and ***P<0.001 (n=3–6). MCAO indicates middle cerebral artery occlusion. Daniel-Christoph Wagner et al. Stroke. 2014;45:623-626 Copyright © American Heart Association, Inc. All rights reserved.

Brain infiltration of leukocytes 24 hours after middle cerebral artery occlusion (MCAO). Brain infiltration of leukocytes 24 hours after middle cerebral artery occlusion (MCAO). A, Infiltration of CD45+ leukocytes, Ly6G+ granulocytes (polymorphonuclear cells [PMN]) and CD3+ T cells. B, Differentiation of CD11b+ myeloid infiltrate by F4/80/MHCII/Ly6C. Major histocompatibility complex (MHC) II+/Ly6C+ cells (Q2) and MHCII–/Ly6C+ cells (Q3) were significantly increased by high-dose granulocyte colony–stimulating factor (GCSF). C, CNS gene expression of cytokines and chemokines was unaltered after GCSF treatment. *P<0.05, **P<0.01, and ***P<0.001 (n=3–6). CCL indicates CC chemokine ligand; CXCL, CXC chemokine ligand; IL, interleukin; TGF, transforming growth factor; and TNF, tumor necrosis factor. Daniel-Christoph Wagner et al. Stroke. 2014;45:623-626 Copyright © American Heart Association, Inc. All rights reserved.