Poststroke Infection and Brain-Induced Immunodepression
Dr. Emsley reported that poststroke infection—commonly urinary tract or respiratory tract infection—appears to occur in up to a third of patients, with most studies reporting adverse functional outcome. “The most consistently reported predictors of poststroke infection seem to be older age, greater baseline severity, total anterior circulation infarction, and dysphagia,” he stated. Other factors may also be at play, as suggested by the incidence of pneumonia in tube-fed patients, including those who have been nil by mouth from the outset, he said. An estimated 10% of deaths following admission for stroke are caused by pneumonia.
According to Dr. Emsley, the concept of “brain-induced immunodepression” (or “poststroke immunodepression”) may help explain observations of spontaneous infections, reduced peripheral blood lymphocyte counts, and impaired T-cell activity occurring poststroke in experimental and clinical settings. “We’re talking about well-regulated brain-immune interactions becoming dysregulated after acute ischemic stroke,” he said.
In their own observations, Dr. Emsley and colleagues have seen reduced capacity of lipopolysaccharides to induce cytokine production by blood cells, as well as a strong inverse correlation with early elevated cortisol concentration. These findings suggest that hypothalamic-pituitary-adrenal axis and sympathetic nervous system activation may have an important role in poststroke immunodepression.
Implications for Clinical Practice
Findings thus far supporting a link between antecedent infection and stroke warrant further investigation of stroke prevention strategies at the time of acute systemic infection. Current and emerging interventions for patients with preceding infection include vaccination (eg, against influenza), treatment with IL-1 receptor antagonist, which targets inflammation via blockade of IL-1, and statin therapy. “We know that statins may protect against endothelial dysfunction,” said Dr. Emsley. In addition, other effects of statins—such as reduced C-reactive protein and a shift in coagulation balance away from the prothrombotic state, as typically seen in sepsis—may ameliorate the increased stroke risk associated with infection. However, “there is some suggestion that statins can be associated with increased poststroke infection very early in the acute phase, but that’s just a slight note of caution,” he said.
For poststroke infection, interventions such as antibiotic therapy may be beneficial. Several recent studies, including the Preventive ANtibacterial THERapy in acute Ischemic Stroke (PANTHERIS) trial, have suggested that preventive therapy with antibiotics may help to reduce infection following severe ischemic stroke. Such studies have also provided additional insight into immunodepressive mechanisms, but further research is needed in this area.
“I think prevention is a key factor,” concluded Dr. Emsley. “This is clearly an area of huge clinical relevance and considerable current research interest.”
—Karen L. Spittler