How Does Prednisone Work?

CrohnoPredOne of the medicines most often prescribed for IBD is prednisone. Most people know it helps reduce inflammation, but there’s lots more to it than that. So how does it work?

Prednisone is in a class of drugs called steroids. ‘Steroid’ is short for ‘steroid hormone’ — ‘steroid’ describes a specific shape of chemical, but ‘hormone’ says more about what the chemical does. A hormone is simply a signal from one part of the body to another, to help regulate various bodily functions.

Steroid hormones come in two kinds, corticosteroids and sex steroids. Sex steroids are produced by reproductive organs, and include testosterone and estrogen. When most people talk about steroids, they mean the synthetic sex hormones that some body-builders use. Prednisone isn’t that kind of steroid, alas.

The other kind of steroid hormones in the body are called ‘corticosteroids’, because they are produced by the adrenal cortex in the adrenal gland. The main hormone produced in the adrenal cortex is called cortisol, often known as the ‘stress hormone’. Cortisol has an important role in metabolism and the immune system, particularly when a person is in an episode of emotional or physical stress. One of the reasons long-term stress is so bad for a person is the consequences of too much cortisol for too long.

Prednisone is a synthetic steroid — that is, not produced in the body — that mimics and works like cortisol. However, prednisone has no effect until your liver converts it into prednisolone (also often prescribed for IBD). Once converted to prednisolone, the hormone can enter the other cells of the body. Inside the cells, it tells the DNA to stop producing certain chemicals (‘transpression’) and to start producing others (‘transactivation’). Where inflammation is concerned, prednisone/prednisolone stops the cell from producing a chemical called ‘intercellular adhesion molecule – 1’ (ICAM-1).

ICAM-1 works in human tissue cells as a landing pad for white blood cells, which then allows those white blood cells to enter tissue and drive the inflammatory response — like IBD in the gut. By limiting the amount of ICAM-1 the cells produce, prednisone/prednisolone keeps those white blood cells from finding a landing pad. Interestingly, ICAM-1 also seems to be a landing pad for the viruses that cause most common colds, allowing that virus to enter tissue as well.

If transpression of ICAM-1 is how prednisone/prednisolone stops inflammation, transactivation seems to be how it creates most of its side effects. The chemicals prednisolone tells the cells to make seem to be why it messes up our sleep and appetites and makes our faces puffy. The same way that long-term cortisol exposure can be very bad, so can long-term therapy with drugs like prednisone.

Of course, we do not know everything about how prednisone works, or why it doesn’t work for everybody — about 16% of IBD patients do not respond to the drug — so more research is needed. Some of that research is aimed at making steroid-like drugs that more selective in their effects, to help limit inflammation without lots of other side effects. Let’s hope they get there soon.

For more basic information on prednisone as a medicine, see this page from the Mayo Clinic.

A relevant article on this subject is Raddatz, D; et al. “Glucocorticoid receptor expression in inflammatory bowel disease: evidence fora mucosal down-regulation in steroid-unresponsive ulcerative colitis”. Alimentary Pharmacology & Therapeutics 19:1 (November 2003).

Photo P1130349C by Flickr user Thirteen of Clubs adapted under Creative Commons license.

 

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