(A) Factors that may contribute to the ability of GCs to shift the balance toward a net pro-inflammatory or antiinflammatory cellular state. An incoherent control system that includes a proinflammatory role for GCs is essential to prevent excessive inflammation and to effectively return to homeostasis. This results in a continuous competition between feedback and feedforward control. (B) The timing of treatment may contribute to the ability of GCs to shift the balance toward a net proinflammatory or antiinflammatory cellular state. This insight is important for critically (re-)evaluating in vitro and/or in vivo studies in which GCs are combined with an inflammatory trigger, here exemplified by LPS, in a laboratory-controlled environment. The order of addition and different durations of stimuli may result in marked differences in, and ongoing competition between, the predominant gene expression signature such as antiinflammatory (green-filled square), proinflammatory (red-filled square), or mixed (red/green-filled square). The expected outcome gene signatures represent the measurement point, where cells are collected and mRNA levels of relevant GC target genes, with pro- and antiinflammatory roles, are determined. The priming effect becomes of particular relevance under circumstances of increased stress prior to the inflammatory insult. Only one example is given here, but many variations in timing are possible.