کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5040603 | 1473902 | 2017 | 16 صفحه PDF | دانلود رایگان |
- Manipulation of the IL-6 system after cerebral ischemia has beneficial potential.
- IL-6 and IL-6R are primarily produced by neurons after cerebral ischemia.
- I.v. adm. IL-6 improves outcome independent of infarct volume in C57BL/6 mice.
- I.v. adm. IL-6 reduces infarct volume and improves outcome in IL-6 KO mice.
Interleukin-6 (IL-6) is a pleiotropic cytokine with neuroprotective properties. Still, the therapeutic potential of IL-6 after experimental stroke has not yet been investigated in a clinically relevant way. Here, we investigated the therapeutic use of intravenously administered IL-6 and the soluble IL-6 receptor (sIL-6R) alone or in combination, early after permanent middle cerebral artery occlusion (pMCAo) in mice. IL-6 did not affect the infarct volume in C57BL/6 mice, at neither 24 nor 72Â h after pMCAo but reduced the infarct volume in IL-6 knockout mice at 24Â h after pMCAo. Assessment of post-stroke behavior showed an improved grip strength after a single IL-6 injection and also improved rotarod endurance after two injections, in C57BL/6 mice at 24Â h. An improved grip strength and a better preservation of sensory functions was also observed in IL-6 treated IL-6 knockout mice 24Â h after pMCAo. Co-administration of IL-6 and sIL-6R increased the infarct volume, the number of infiltrating polymorphonuclear leukocytes and impaired the rotarod endurance of C57BL/6 mice 24Â h after pMCAo. IL-6 administration to naïve C57BL/6 mice lead after 45Â min to increased plasma-levels of CXCL1 and IL-10, whereas IL-6 administration to C57BL/6 mice lead to a reduction in the ischemia-induced increase in IL-6 and CXCL1 at both mRNA and protein level in brain, and of IL-6 and CXCL1 in serum. We also investigated the expression of IL-6 and IL-6R after pMCAo and found that cortical neurons upregulated IL-6 mRNA and protein, and upregulated IL-6R after pMCAo. In conclusion, the results show a complex but potentially beneficial effect of intravenously administered IL-6 in experimental stroke.
Journal: Brain, Behavior, and Immunity - Volume 65, October 2017, Pages 296-311