Glucocorticoids may be used in low doses in
adrenal insufficiency. In much higher doses, oral or inhaled glucocorticoids are used to suppress various
allergic,
inflammatory, and autoimmune disorders. Inhaled glucocorticoids are the second-line treatment for
asthma. They are also administered as post-transplantory immunosuppressants to prevent the
acute transplant rejection and the
graft-versus-host disease. Nevertheless, they do not prevent an infection and also inhibit later
reparative processes. Newly emerging evidence showed that glucocorticoids could be used in the treatment of
heart failure to increase the renal responsiveness to diuretics and natriuretic peptides. Glucocorticoids are historically used for pain relief in inflammatory conditions. However, corticosteroids show limited efficacy in pain relief and potential adverse events for their use in
tendinopathies.
Replacement Any glucocorticoid can be given in a dose that provides approximately the same glucocorticoid effects as normal
cortisol production; this is referred to as physiologic, replacement, or maintenance dosing. This is approximately 6–12 mg/m2/day of hydrocortisone (m2 refers to
body surface area (BSA), and is a measure of body size; an average man's BSA is 1.9 m2).
Therapeutic immunosuppression Glucocorticoids cause
immunosuppression, and the therapeutic component of this effect is mainly the decreases in the function and numbers of
lymphocytes, including both
B cells and
T cells. The major mechanism for this immunosuppression is through inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (
NF-κB). NF-κB is a critical transcription factor involved in the synthesis of many mediators (i.e., cytokines) and proteins (i.e., adhesion proteins) that promote the immune response. Inhibition of this transcription factor, therefore, blunts the capacity of the immune system to mount a response. Glucocorticoids, however, not only reduce T cell proliferation, but also lead to another well known effect – glucocorticoid-induced apoptosis. The effect is more prominent in immature T cells still inside in the thymus, but peripheral T cells are also affected. The exact mechanism regulating this glucocorticoid sensitivity lies in the
Bcl-2 gene. Glucocorticoids also suppress the
humoral (antibody-mediated) immunity, thereby causing a
humoral immune deficiency. Glucocorticoids cause
B cells to express smaller amounts of
IL-2 and of
IL-2 receptors. This diminishes both B cell clone expansion and
antibody synthesis. The diminished amounts of IL-2 also cause fewer T lymphocyte cells to be activated. The effect of glucocorticoids on
Fc receptor expression in immune cells is complicated. Dexamethasone decreases
IFN-γ stimulated
Fc gamma RI expression in
neutrophils while conversely causing an increase in
monocytes. Glucocorticoids may also decrease the expression of
Fc receptors in macrophages, but the evidence supporting this regulation in earlier studies has been questioned. The effect of
Fc receptor expression in
macrophages is important since it is necessary for the
phagocytosis of
opsonised cells. This is because Fc receptors bind
antibodies attached to cells targeted for destruction by macrophages.
Anti-inflammatory Glucocorticoids are potent anti-inflammatories, regardless of the inflammation's cause; their primary anti-inflammatory mechanism is
lipocortin-1 (annexin-1) synthesis. Lipocortin-1 both suppresses
phospholipase A2, thereby blocking
eicosanoid production, and inhibits various
leukocyte inflammatory events (
epithelial adhesion,
chemotaxis,
phagocytosis,
respiratory burst, etc.). In other words, glucocorticoids not only suppress immune response, but also inhibit the two main products of inflammation,
prostaglandins and
leukotrienes. They inhibit prostaglandin synthesis at the level of
phospholipase A2 as well as at the level of
cyclooxygenase/PGE isomerase (COX-1 and COX-2), the latter effect being much like that of
NSAIDs, thus potentiating the anti-inflammatory effect. In addition, glucocorticoids also suppress
cyclooxygenase expression. Glucocorticoids marketed as anti-inflammatories are often topical formulations, such as nasal sprays for
rhinitis or
inhalers for
asthma. These preparations have the advantage of only affecting the targeted area, thereby reducing side effects or potential interactions. In this case, the main compounds used are
beclometasone,
budesonide,
fluticasone,
mometasone and
ciclesonide. In rhinitis, sprays are used. For asthma, glucocorticoids are administered as
inhalants with a
metered-dose or
dry powder inhaler. In rare cases, symptoms of
Radiation-induced thyroiditis has been treated with oral glucocorticoids.
Hyperaldosteronism Glucocorticoids can be used in the management of
familial hyperaldosteronism type 1. They are not effective, however, for use in the type 2 condition.
Heart failure Glucocorticoids could be used in the treatment of decompensated heart failure to potentiate renal responsiveness to diuretics, especially in heart failure patients with refractory diuretic resistance with large doses of loop diuretics. == Resistance ==