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How Do Steroids Cause Immunosuppression?

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Glucocorticoids (GCs, “steroids”) are routinely used to induce immunosuppression in patients who have received transplants or have autoimmune diseases. However, we often see an increase in the measured white blood cell (WBC) count after steroid administration. Let’s explore this further.

Genes within the DNA genome are transcribed into messenger (mRNA) which is subsequently translated into proteins by ribosomes. Steroids promote the transcription of anti-inflammatory genes while inhibiting inflammatory interleukins such as IL-1. Furthermore, mRNA that happens to still be transcribed for GM-CSF, TNF, and inflammatory interleukins is rendered more unstable in the presence of steroids.

White blood cells (WBCs) normally roll along endothelial adhesion proteins (ie, selectins) looking for signals such as infection or tissue damage. Upon activation, they transmigrate through the endothelium into the region of interest. Steroids degrade these adhesion proteins causing more WBCs to demarginate off the endothelial walls into free flowing circulation. WBC trafficking from the endothelium into the tissues is therefore altered. This demargination effect coupled with the release of immature WBCs from the bone marrow by steroids explains why we see an apparent increase in WBC. Remember, to a large extent, the true “WBC count” hasn’t increased. They have just shifted compartments from extravascular tissues back into the plasma where we measure their concentrations and morphologies (ie, on a CBC).

Less trafficking of WBCs into inflamed/infected tissues + decreased proinflammatory interleukin/cytokine production + increased anti-inflammatory gene transcription = immunosuppression.

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