Catecholamine-induced interleukin-10 release: a key mechanism in systemic immunodepression after brain injury

BACKGROUND: Infections after severe brain injury or polytrauma are still a problem, and may be the result of a brain-mediated disturbed systemic immunoreactivity. The mechanism that connects initial brain affection and systemic immunodepression, however, is still poorly understood. REVIEW: In order to analyze the influence of the sympathetic nervous system in the context of brain injury on systemic immune functions, we performed various in vitro, in vivo and clinical studies. We were able to demonstrate that catecholamines trigger the release of the strong anti-inflammatory cytokine interleukin (IL)-10 from peripheral blood mononuclear cells and monocytes. In animal models we were able to show that increased intracranial pressure as well as intracerebral proinflammatory cytokines (eg IL-1β) produce a rapid systemic IL-10 release through sympathetic activation. Thus, in both models, the predominant role of catecholamines for this effect was confirmed by the complete prevention of IL-10 increase after β-adrenoreceptor blockade. Moreover, in clinical studies we clearly demonstrated that neurosurgical procedures involving brain-stem manipulation invoke sympathetic activation and a rapid systemic IL-10 release. Remarkably, this was associated with monocytic deactivation – a sign of systemic immunodepression and a high risk of infectious complications.Finally, these data were validated in patients with accidental brain injury, in whom we demonstrated a correlation between the severity of injury, sympathetic activation, IL-10 plasma levels and the incidence of infectious complications. CONCLUSION: In summary, we suppose that activation of inhibitory neuroimmune pathways like the sympathetic nervous system, but also the hypothalamic-pituitary-adrenal axis, may trigger a systemic anti-inflammatory response syndrome that leads to systemic immunodepression. In this process the catecholamine-mediated systemic IL-10 release that causes monocytic deactivation may be a key mechanism.