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. 
The 4 mg/mL injection strength may be used for intralesional and soft tissue administration. Doses range from mg to 4 mg injected as a single dose at the appropriate site. For soft tissue and bursal injections a dose of 2 to 4 mg is recommended. Ganglia require a dose of 1 to 2 mg. A dose of to 1 mg is used for injection into tendon sheaths. Usually employed when condition to be treated is limited to 1 or 2 sites. Dosage dependent upon degree of inflammation, size, disease state, and location of affected area. Repeat doses may be given from once every 3 to 5 days to once every 2 to 3 weeks.