Adrenergic modulation of neutrophil and macrophage functions: pathophysiological cues

In this review, we will summarize current and past findings on the adrenergic regulation of myeloid cell functions and dynamics, with special emphasis on the pathophysiological impact of such modulation. Adrenergic signaling has traditionally been described to be immunosuppressive, but some recent results are challenging this paradigm, in particular those related to in vivo models of stress and findings in human patients. Also, cumulative evidence reveals that the final pro- or anti-inflammatory outcome of adrenergic inputs in myeloid cells appears to be very dependent on the experimental setup utilized or on the cellular context (resting vs stimulated conditions, in vivo vs in vitro settings, mice vs human cells, health vs pathology). Varying doses and/or time points may result in seemingly contradictory results that depend on the nature of receptor engaged (α or β adrenergic receptor subtypes), the downstream cascades involved, the presence of additional stimulatory or inhibitory signals, and the actual kinetics of the process studied. We will thus address some of these apparently paradoxical findings, review several pathological settings in which adrenergic modulation of neutrophil or macrophage-mediated immunity is relevant, and discuss open questions that still remain unanswered.