"Your immune system begins to react to something - a virus or allergen or bacteria or such and something triggers that immune process to dial it up - and it doesn't get a signal to stop. So now your immune process is in overdrive and the mechanism to slow it down is stuck."

I like this explanation! It sounds like reactive arthritis to me.

Endogenous cortisol from the adrenals is supposed to regulate inflammation ... not prednisone. Maybe the adrenals get overwhelmed by the excess amount of inflammation when the immune process goes into overdrive. Maybe the adrenals can't produce enough cortisol relative to the amount of inflammation. Prednisone works because it floods our body with exogenous synthetic cortisol.

Too much endogenous cortisol and exogenous synthetic cortisol causes an oversupply of corticosteroid. This causes a problem because too much corticosteroid is just as bad as not enough. If we persist with taking prednisone the adrenals take a holiday. The adrenals shut down the production of cortisol in an attempt to restore the proper amount corticosteroid.

The whole system that regulates inflammation (HPA axis) gets screwed up the longer we take prednisone. It isn't just inflammation that is regulated by the HPA axis --there are other things that become unregulated. My blood pressure and cholesterol levels went through the roof for example.

When the adrenals don't function, a major malfunction ensues.