Neutrophil polarization by IL-27 as a therapeutic target for intracerebral hemorrhage

Xiurong Zhao, Shun-Ming Ting, Chin-Hsuan Liu, Guanghua Sun, Marian Kruzel, Meaghan Roy-O’Reilly and Jaroslaw Aronowski ()
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Xiurong Zhao: University of Texas Health Science Center at Houston, McGovern Medical School
Shun-Ming Ting: University of Texas Health Science Center at Houston, McGovern Medical School
Chin-Hsuan Liu: University of Texas Health Science Center at Houston, McGovern Medical School
Guanghua Sun: University of Texas Health Science Center at Houston, McGovern Medical School
Marian Kruzel: University of Texas Health Science Center at Houston, McGovern Medical School
Meaghan Roy-O’Reilly: University of Texas Health Science Center at Houston, McGovern Medical School
Jaroslaw Aronowski: University of Texas Health Science Center at Houston, McGovern Medical School

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: Abstract Shortly after intracerebral hemorrhage, neutrophils infiltrate the intracerebral hemorrhage-injured brain. Once within the brain, neutrophils degranulate, releasing destructive molecules that may exacerbate brain damage. However, neutrophils also release beneficial molecules, including iron-scavenging lactoferrin that may limit hematoma/iron-mediated brain injury after intracerebral hemorrhage. Here, we show that the immunoregulatory cytokine interleukin-27 is upregulated centrally and peripherally after intracerebral hemorrhage. Data from rodent models indicate that interleukin-27 modifies neutrophil maturation in the bone marrow, suppressing their production of pro-inflammatory/cytotoxic products while increasing their production of beneficial iron-scavenging molecules, including lactoferrin. Finally, interleukin-27 or lactoferrin administration results in reduced edema, enhanced hematoma clearance, and improved neurological outcomes in an animal model of intracerebral hemorrhage. These results suggest that interleukin-27/lactoferrin-mediated modulations of neutrophil function may represent a therapeutically viable concept for the modification of neutrophils toward a “beneficial” phenotype for the treatment of intracerebral hemorrhage.

Date: 2017
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DOI: 10.1038/s41467-017-00770-7

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