Sex differences and the role of IL-10 in ischemic stroke recovery

Biology of Sex Differences

Sarah E. Conway¹  Meaghan Roy-O’Reilly³  Brett Friedler²  Ilene Staff⁴  Gilbert Fortunato⁴  Louise D. McCullough³ 

[1] New York University School of Medicine, New York 10016, NY, USA

[2] Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington 06030, CT, USA

[3] Department Of Neurology and Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington 06030, CT, USA

[4] Research Program, Hartford Hospital, 80 Seymour Street, Hartford 06106, CT, USA

关键词: Inflammation;    Cytokines;    IL-10;    Sex differences;    Stroke;   

Others  :  1229660
DOI  :  10.1186/s13293-015-0035-9

 received in 2015-06-30, accepted in 2015-08-20,  发布年份 2015

【 摘 要 】

Females experience poorer recovery after ischemic stroke compared to males, even after controlling for age and stroke severity. IL-10 is an anti-inflammatory cytokine produced by T regulatory cells and Th2 CD4 ⁺helper T cells. In ischemic stroke, an excessive IL-10 response contributes to post-stroke immunosuppression, which worsens outcomes. However, it is unknown if sex differences exist in IL-10 levels after ischemic stroke. In this study, we found that higher levels of IL-10 were associated with poor acute and long-term outcomes after ischemic stroke in female patients but not in males. After controlling for confounders, IL-10 was not an independent predictor of functional outcomes. This suggests that higher serum IL-10 levels may reflect factors that interact with sex such as age and stroke severity.

【 授权许可】

   
2015 Conway et al.

【 参考文献 】

• [1]Bushnell C, McCullough LD, Awad IA, Chireau MV, Fedder WN, Furie KL et al.. Guidelines for the prevention of stroke in women: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014; 45:1545-88.
• [2]Howe MD, McCullough LD. Prevention and management of stroke in women. Expert Rev Cardiovasc Ther. 2015; 13:403-15.
• [3]Reeves MJ, Bushnell CD, Howard G, Gargano JW, Duncan PW, Lynch G et al.. Sex differences in stroke: epidemiology, clinical presentation, medical care, and outcomes. Lancet Neurol. 2008; 7:915-26.
• [4]Reeves MJ, Fonarow GC, Zhao X, Smith EE, Schwamm LH. Get With The Guidelines-Stroke Steering Committee & Investigators. Quality of care in women with ischemic stroke in the GWTG program. Stroke. 2009; 40:1127-33.
• [5]Paradiso S, Robinson RG. Gender differences in poststroke depression. J Neuropsychiatry Clin Neurosci. 1998; 10:41-7.
• [6]Chen Y, Won SJ, Xu Y, Swanson RA. Targeting microglial activation in stroke therapy: pharmacological tools and gender effects. Curr Med Chem. 2014; 21:2146-55.
• [7]Dirnagl U, Klehmet J, Braun JS, Harms H, Meisel C, Ziemssen T et al.. Stroke-induced immunodepression: experimental evidence and clinical relevance. Stroke. 2007; 38:770-3.
• [8]Iadecola C, Anrather J. The immunology of stroke: from mechanisms to translation. Nat Med. 2011; 17:796-808.
• [9]Worthman H, Tryc A, Dirks M, Schuppner R, Brand K, Klawonn F et al.. Lipopolysaccharide binding protein, interleukin-10, interleukin 6 and C-reactive protein blood levels in acute ischemic stroke patients with post-stroke infection. J Neuroinflammation. 2015; 12:13. BioMed Central Full Text
• [10]Njemini R, Bautmans I, Onyema O, Van Puyvelde K, Demanet C, Mets T. Circulating heat shock protein 70 in health, aging and disease. BMC Immunol. 2011;12:24.
• [11]Bartlett DB, Firth CM, Phillips AC, Moss P, Baylis D, Sydall H et al.. The age-related increase in low-grade systemic inflammation (inflammaging) is not driven by cytomegalovirus infection. Aging Cell. 2012; 11:912-5.
• [12]Dehlendorff C, Andersen KK, Olsen TS. Sex disparities in stroke: women have more severe strokes but better survival than men. J Am Heart Assoc. 2015; 4: Article ID e001967
• [13]Li B, Wang T, Lou Y, Guo X, Gu H, Zhu Y, et al. Sex differences in outcomes and associated risk factors after acute ischemic stroke in elderly patients: a prospective follow-up study. J Stroke Cerebrovasc Dis. 2015.
• [14]Banerjee A, Wang J, Bodhankar S, Vandenbark AA, Murphy SJ, Offner H. Phenotypic changes in immune cell subsets reflect increased infarct volume in male vs. female mice. Transl Stroke Res. 2013; 4:554-63.
• [15]Wang M, Baker L, Tsai B, Meldrum K, Meldrum D. Sex differences in the myocardial inflammatory response to ischemia-reperfusion injury. Am J Physiol Endocrinol Metab. 2005; 288:E321-6.
• [16]Schröder J, Kahlke V, Staubach K, Zabel P, Stüber F. Gender differences in human sepsis. Arch Surg. 1998; 133:1200-5.
• [17]Yan FL, Zhang JH. Role of the sympathetic nervous system and spleen in experimental stroke-induced immunodepression. Med Sci Monit. 2014; 20:2489-96.
• [18]Arponen O, Muuronen A, Taina M, Sipola P, Hedman M, Jäkälä P et al.. Acute phase IL-10 plasma concentration associates with high risk sources of cardiogenic stroke. PLos One. 2015; 10: Article ID e0120910
• [19]Palm F, Urbanek C, Wolf J, Buggle F, Kleemann T, Hennerici MG, et al. Etiology, risk factors and sex differences in ischemic stroke in the Ludwigshafen stroke study, a population-based stroke registry. Cerebrovasc Dis. 2012;33:69–75.
• [20]Chamorro A, Urra X, Planas A. Infection after acute ischemic stroke. A manifestation of brain-induced immunodepression. Stroke. 2007; 38:1097-103.
• [21]Kammersgaard LP, Jorgensen HS, Reith J, Nakayama H, Houth JG, Weber UJ, et al. Early infection and prognosis after acute stroke: the Copenhagen stroke study. J Stroke Cerebrovasc Disease. 2001;10:217–21.