The second major complication is a steroid related rise in eye pressure, also known as being a "steroid responder". This usually requires at least 2 weeks of continuous steroid use, and is reversible if the steroid is discontinued. The rise in pressure can be very high but if often asymptomatic. It may be more common in people already being treated for glaucoma. If a person has glaucoma or has a history of steroid related eye pressure problems, they should consult with an ophthalmologist for monitoring of eye pressure if steroid treatment is being contemplated.
When activated macrophages start to secrete IL-1, which synergistically with CRH increases ACTH,  T-cells also secrete glucosteroid response modifying factor (GRMF), as well as IL-1; both increase the amount of cortisol required to inhibit almost all the immune cells.  Immune cells then assume their own regulation, but at a higher cortisol setpoint. The increase in cortisol in diarrheic calves is minimal over healthy calves, however, and falls over time.  The cells do not lose all their fight-or-flight override because of interleukin-1's synergism with CRH. Cortisol even has a negative feedback effect on interleukin-1  —especially useful to treat diseases that force the hypothalamus to secrete too much CRH, such as those caused by endotoxic bacteria. The suppressor immune cells are not affected by GRMF,  so the immune cells' effective setpoint may be even higher than the setpoint for physiological processes. GRMF affects primarily the liver (rather than the kidneys) for some physiological processes.