Figure 1

Mechanism of the brain injury-induced interleukin (IL)-10 release that leads to systemic immunodepression. Proinflammatory cytokines are produced in the brain after infection, injury and ischaemia. Microglia, astrocytes and blood-derived immune cells are the main sources for this cytokine production. These brain cytokines (especially IL-1β) and/or an increased intracranial pressure (ICP) may activate inhibitory neuroimmune pathways, such as the sympathetic nervous system. This leads to high catecholamine levels in plasma. Immune cells, especially monocytes, carry β-adrenoreceptors on their surface that mediate the catecholamine-induced increase of intracellular levels of cyclic adenosine monophosphate (cAMP) as second messenger for the regulation of monocytic cytokine production. Thus, catecholamines and cyclic AMP-elevating drugs can inhibit the production of IL-1β, IL-12 heterodimer and tumour necrosis factor (TNF)-α and increase the synthesis of the potent anti-inflammatory and immunosuppressive cytokine IL-10, resulting in the downregulation of monocytic proinflammatory and accessory functions. By this mechanism, catecholamines may switch the monocytes/macrophages to a predominant anti-inflammatory action. HLA, human leukocyte antigen.