It is evidence that dissociated SRC is responsible for inhibiting the release of arachidonic acid (AA) from cell membrane phospholipids. AA is required for the synthesis of inflammatory mediators (prostaglandins and leukotrienes) and thus AA inhibition mediates several important pathways such as cellular growth, metabolism and inflammation. Previous studies identified mGRs in lymphoma cells, but it wasn't until 2004 that mGRs were identified in human peripheral mononuclear cells. The prevalence of mGRs ranges per cell type, with the highest concentration in B lymphocytes at up to 12.3%, up to 9.2% in monocytes, and absent from T lymphocytes. Studies have shown a positive correlation between the mGR-positive cells and disease related activity. There are no proven signaling pathways associated with mGR at this time. Some researchers hypothesize that high disease activity activates mGR expression and upon administering methylprednisolone, creates a negative feedback loop by inducing apoptosis. High concentrations of methylprednisolone intercalate in plasma and mitochondrial cellular membranes. This association changes physiochemical properties of the membrane; activating membrane proteins, altering cellular functions and ultimately influencing cation transport through the plasma membrane and stimulating the proton leak across the inner mitochondrial membrane. Hindered oxidative phosphorylation compromises ATP production, a major energy source for cellular energy metabolism and immune function. In vivo studies of Con-A stimulated thymocytes (in rats) and human immune cells that were administered high doses of methylprednisolone has been shown to inhibit respiration in a dose-dependent manner, inhibit plasma calcium and sodium uptake, and increase cytoplasmic calcium concentration. The summative process is as follows: Methylprednisolone intercalates in the plasma membrane, causes physiochemical changes, activates membrane proteins that inhibit plasma calcium and sodium uptake (mimicking an energy deficit state). ATP consumption drops (resembled by inhibited respiration), resulting in protein permeability at the inner mitochondrial membrane and uncoupling of oxidative phosphorylation. Of notable importance, DNA/RNA synthesis was not hindered. The dependency of house keeping cells and immune cells on ATP, results in immunosuppression during ATP deficit. Specific immune functions effected by this process are cytokinesis, migration, phagocytosis, antigen processing and presenting, antibody synthesis, cytotoxicity and regulation. The HPA The activation of the hypothalamic-pituitary axis (HPA) stimulates the production of endogenous glucocorticoids within the adrenal cortex. The HPA interprets stimuli (stress, inflammation and circadian cues) and transduces a corresponding physiochemical response. Glucocorticoids released in the blood, serve as a messenger by binding to glucocorticoid receptors in a wide distribution across the body, including the