Background and Purpose Immune responses to brain antigens occur after stroke, and experimental studies show that the likelihood of developing a detrimental autoimmune response to these antigens is increased by systemic inflammation at the time of stroke. The aim of this study was to determine if patients who developed infection in the post-stroke period would be similarly predisposed to develop autoimmune responses to central nervous system (CNS) antigens. Methods We enrolled 114 patients within 72 hours of ischemic stroke. Clinical and demographic data were obtained, and cellular immune responses to a panel of CNS antigens were assessed during the initial week and again at day 90. Outcome was assessed using the modified Rankin Scale. Results Patients who developed an infection, especially pneumonia, in the 15 days after stroke were more likely to evidence a TH1(+) response to myelin basic protein (MBP) and glial fibrillary acidic protein (P=0.019 and P=0.039, respectively) at 90 days after stroke. Further, more robust TH1 responses to MBP at 90 days were associated with a decreased likelihood of good outcome, even after adjusting for baseline stroke severity and patient age (Odds Ratio = 0.477, 95% CI = 0.244–0.935; P=0.031). Conclusion This study demonstrates that immune responses to brain antigens occur after stroke. And while these responses are likely to be an epiphenomenon of ischemic brain injury, the response to MBP appears to have clinical consequences. The potential role of post-ischemic autoimmune mediated brain injury deserves further investigation.

Background and purpose Animals subjected to an inflammatory insult with lipopolysaccharide (LPS) at the time of stroke are predisposed to develop a detrimental autoimmune response to myelin basic protein (MBP). In this study, we sought to determine whether other inflammatory stimuli could similarly invoke central nervous system (CNS) autoimmunity and whether these detrimental autoimmune responses occurred to antigens other than MBP. Methods Male Lewis rats underwent 3 h middle cerebral artery occlusion (MCAO) and received intraperitoneal injections of LPS, staphylococcal enterotoxin B (SEB), lipoteichoic acid (LTA) or saline at the time of reperfusion. Behavioral tests were performed at set time intervals after MCAO and animals were sacrificed at 1 month to analyze the immune response to MBP, neuron specific enolase (NSE) and proteolipid protein (PLP). Results Lymphocytes from SEB treated animals were highly reactive to all tested CNS antigens, but treatment with LPS was most likely to lead to a Th1(+) response. A Th1(+) response to MBP, NSE or PLP in spleen was associated with worse outcome, although the response to NSE was most predictive of poor outcome. Animals with a cell mediated autoimmune response to either MBP or NSE in spleen had a concomitant humoral response to these antigens. Conclusions These data show that LPS, but not other inflammatory stimuli, increase the likelihood of developing a detrimental autoimmune response to an array of brain antigens.

Background Infection is common following stroke and is independently associated with worse outcome. Clinical studies suggest that infections occur more frequently in those individuals with stroke-induced immunologic dys-function. This study sought to explore the contribution of immunomodulatory cytokines and hormones to lymphocyte function and infection risk. Methods Patients (N = 112) were enrolled as soon as possible after the onset of ischemic stroke. Blood was drawn to assess plasma cortisol, IL-10, IL-1ra, lymphocyte numbers, and lymphocyte function at 72 h after stroke onset; infections were censored through 21 days after stroke onset. Results Infection occurred in 25% of patients. Stroke severity was the most important predictor of infection risk. Increased plasma cortisol, IL-10, and IL-1ra, as well as decreased lymphocyte numbers, at 72 h after stroke onset were associated with risk of subsequent infection. After controlling for stroke severity, only IL-1ra was independently associated with infection risk, and the degree of risk was consistent throughout the post-stroke period. Infection, but not IL-1ra itself, was associated with worse outcome at 3 months. Conclusions In this study cohort, increased plasma IL-1ra was independently associated with the risk of post-stroke infection. Further studies are needed to validate this finding, which could have important implications for stroke therapy.