Glucocorticoids Resolve Inflammation and Restore Homeostasis.

[Ema]

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667973/pdf/nihms434528.pdf

As a pharmacological intervention, glucocorticoids are the first line of defense to treat chronic inflammatory diseases. However, how to reconcile the physiological role of glucocorticoids as major factors released in response to stress (inflammation included) with their anti-inflammatory actions is a question that remains to be resolved.

The ability of molecules to have both a pro- and anti-inflammatory role in both normal physiological and pathological conditions is not unprecedented. For example, both IL-6 and leptin are known to have pro- and anti-inflammatory properties [63-65]. It is becoming clear that the actions of glucocorticoids are much more pleiotropic than previously thought, and thus cannot be simply categorized as antiinflammatory (Figure 5).

The regulation of components of the innate immune system, namely TLR2, NLRP3, and P2Y2R [22,24,25], provides evidence that glucocorticoids ready the immune system to respond quickly to both bacterial infection and tissue damage.

In addition, the complete absence of glucocorticoids (i.e., adrenalectomy) renders animals much more susceptible to LPS-induced systemic inflammation [66], suggesting that glucocorticoids are necessary both to respond to infection as well as to prevent a massive release of cytokines and prevent the adaptive immune system from over-reacting.