Methylprednisolone is a systemic synthetic corticosteroid, which, just as the naturally occurring glucocorticoids, exerts a wide range of physiologic effects. Clinical use of methylprednisolone is mainly due to its anti-inflammatory and immunosuppressive activity in the human body.

Labeled indications of methylprednisolone subcategorize by its use in different organ systems:

• In dermatology, it has utility in the management of atopic dermatitis,[1] contact dermatitis,[2] pemphigus vulgaris and foliaceus.[3] bullous pemphigus,[4] erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis.[5]
• In endocrinology, it is used in the management of congenital adrenal hyperplasia,[6] hypercalcemia associated with cancer,[7] and as a second-line treatment in conjunction with mineralocorticoids for primary or secondary adrenocortical insufficiency.
• In gastroenterology, methylprednisolone its use is for acute exacerbations of inflammatory bowel disease.[8]
• In hematology, it serves in the treatment of autoimmune hemolytic anemia,[9] congenital (erythroid) aplastic anemia,[10] and immune thrombocytopenia.[11]
• In neurology, it is the mainstay therapy in acute exacerbations of multiple sclerosis.[12]
• In ophthalmology, it is a therapeutic choice in severe allergic and inflammatory processes of the eye and its adnexa, such as uveitis, scleritis, chorioretinitis, iritis and iridocyclitis, keratitis, optic neuritis, retinal vasculitis, and allergic conjunctivitis.[13]
• In nephrology, it is helpful in the management of nephrotic syndrome, idiopathic type,[14] or secondary to lupus nephritis.[15]
• In pulmonology, its indications include aspiration pneumonitis,[16] asthma,[17] chronic beryllium disease, as an adjunct to antituberculous chemotherapy in disseminated pulmonary tuberculosis, in eosinophilic pneumonia,[18] and symptomatic sarcoidosis.[19]
• In rheumatology, it has indications for the management of acute rheumatic carditis,[20] acute gout,[21] ankylosing spondylitis,[22] dermatomyositis and polymyositis,[23] psoriatic arthritis,[24] and rheumatoid arthritis, including the juvenile type,[25] and systemic lupus erythematosus.[26]

Other miscellaneous labeled indications for methylprednisolone include:

• Intraarticular and soft tissue administration in acute gouty arthritis, acute and subacute bursitis, acute tenosynovitis, epicondylitis, and synovitis of osteoarthritis.[27][28]
• Intralesional administration in alopecia areata,[29] discoid lupus erythematosus,[30] keloid disease,[31] and lichen planus.[32]

Off-label indications of methylprednisolone include:

• Adjunct therapy for acute spinal cord injury
• Moderate to severe acute distress respiratory syndrome and severe alcoholic hepatitis
• As a preventive agent in bronchiolitis obliterans syndrome
• Hormonal resuscitation in cadaveric organ recovery
• Treatment of acute cellular and antibody-mediated rejection in cardiac transplant
• Adjunct in the management of acute exacerbation of chronic obstructive pulmonary disease
• Severe/refractory nausea and vomiting of pregnancy
• Adjunct treatment of Pneumocystis pneumonia in HIV-infected patients
• As palliation alternative in castration-resistant metastatic prostate cancer

Methylprednisolone and its derivatives, methylprednisolone acetate succinate, and methylprednisolone sodium, are intermediate-acting, synthetic glucocorticoids used mainly as anti-inflammatory or immunosuppressive agents. Methylprednisolone is five times more potent in its anti-inflammatory properties relative to hydrocortisone (cortisol), with minimal mineralocorticoid activities compared to the latter.[33]

Methylprednisolone diffuses passively across the cellular membrane and binds to the intracellular glucocorticoid receptor. This complex translocates into the nucleus, where it interacts with specific DNA sequences, resulting in either enhancement or suppression of transcription of particular genes. The methylprednisolone-glucocorticoid receptor complex binds and blocks promoter sites of proinflammatory genes,[34] promotes expression of anti-inflammatory gene products,[35] and inhibits the synthesis of inflammatory cytokines, mainly by blocking the function of transcription factors, such as nuclear factor-kappa-B (NF-kB).[36]

Methylprednisolone, like the rest of the corticosteroids, also suppresses the synthesis of cyclooxygenase (COX)-2, responsible for the production of prostaglandins in damaged tissue, leading to the inflammation cascade.[37]

By reversing capillary permeability, suppressing the migration of fibroblasts and polymorphonuclear leukocytes, controlling the rate of protein synthesis, and stabilizing lysosomes, at the cellular level, methylprednisolone may control or prevent inflammation through these actions as well.

Methylprednisolone inhibits cell-mediated immunologic functions, especially those dependent on lymphocytes. Glucocorticoid administration results in a neutrophilic leukocytosis, smaller elevations in monocytes, dramatic reductions in circulating eosinophils, and lesser reductions in lymphocytes. The use of methylprednisolone and other glucocorticoids results in a reduced ability of leukocytes to adhere to vascular endothelium and exit from the circulation. Glucocorticoids impair a variety of T cell functions, and moderate-to-high doses induce T cell apoptosis while keeping B cell function and antibody production preserved.[38]

Tissue-specific responses to steroids can occur by the presence in each tissue of specific protein regulators controlling the interaction between the hormone-receptor complex and particular DNA response elements. This activity leads to a wide array of gene expression and physiological responses by corticosteroids.

Some of the most important effects of methylprednisolone and the rest of the corticosteroids are the result of homeostatic responses by insulin and glucagon. Glucocorticoids stimulate gluconeogenesis, which results in elevated blood glucose, catabolism of muscle protein, and stimulation of insulin secretion. Both lipolysis and lipogenesis become stimulated, with a net increase of fat deposition in certain areas (e.g., face, shoulders, and back).[39]

Methylprednisolone and the rest of the glucocorticoids cause muscle protein catabolism. Also, lymphoid and connective tissue, fat, and skin undergo wasting under the influence of high concentrations of these steroids. Catabolic effects on the bone can lead to osteoporosis. In children, growth inhibition takes place.

Methylprednisolone may be administered orally with food or milk to decrease gastrointestinal adverse effects. Administration may also be intramuscularly or intravenously. When administered intramuscularly (in the form of methylprednisolone acetate or succinate), administration should not be into the deltoid muscle due to evidence of subcutaneous atrophy. Injections into the dermis should be avoided, and injection should not be into areas that have evidence of acute local infection.

Intravenous administration of methylprednisolone (in the form of methylprednisolone succinate) is rate dependent upon the dose and severity of the condition. Most commonly, with intermittent infusion, methylprednisolone is administered over 15 to 60 minutes. The administration of large doses should be over at least 30 to 60 minutes. 

There are reports of hypotension, cardiac arrhythmias, and sudden death when methylprednisolone administration occurs under 30 minutes in doses greater or equal than 250 mg.[40]

The onset of action of intravenous methylprednisolone succinate is within 1 hour, while intra-articular administration of IV acetate is of 1 week, with a duration of 1 to 5 weeks. Methylprednisolone has an oral bioavailability of 88% approximately. The half-life elimination of intravenous methylprednisolone is of 0.25 hours, with an oral half-life of 2-5 hours. It has hepatic metabolism and undergoes urinary excretion.[41][42]

The significant undesirable effects of glucocorticoids result from their hormonal actions, which lead to the clinical picture of iatrogenic Cushing syndrome. Facial rounding, puffiness, fat deposition, and plethora usually appear (moon facies). Fat tends to redistribute from the extremities to the trunk, the back of the neck, and the supraclavicular fossae. There is increased growth of fine hair on the face, thighs, and trunk.  Steroid-induced punctate acne may appear, and insomnia and increased appetite are also effects.

With concurrent use of methylprednisolone, protein catabolism will continue, diverting amino acids to glucose production, thus increasing the need for insulin and over time resulting in weight gain. Myopathy and muscle wasting can occur, as well as thinning of the skin, with striae and bruising. Hyperglycemia and eventually osteoporosis can develop, as well as diabetes and aseptic necrosis of the hip.[43]

A more detailed way to review the adverse effects of methylprednisolone and other corticosteroids is by classifying them based on the different organ systems affected:

• Dermatologic and side effects in appearance include skin thinning and ecchymoses, Cushingoid features, and weight gain.
• Ophthalmologic side effects include the formation of cataracts, the increase of intraocular pressure, and the development of exophthalmos.
• Cardiovascular side effects include fluid retention and hypertension, premature atherosclerotic disease, arrhythmias, and possible hyperlipidemia.
• Gastrointestinal effects include the increased risk of gastritis, ulcer formation, and gastrointestinal bleeding. 
• Bone and muscle effects include osteoporosis, osteonecrosis, and myopathy.
• Neuropsychiatric side effects include mood disorders, psychosis, and memory impairment.
• Metabolic and endocrine side effects consist of hyperglycemia and hypothalamic-pituitary-adrenal axis suppression.
• Immune system effects include increased susceptibility of infections.
• Hematologic side effects include leukocytosis and neutrophilia.

Methylprednisolone contraindications include patients with documented hypersensitivity to the drug or components, systemic fungal infection, intrathecal administration, live or attenuated virus vaccine, idiopathic thrombocytopenia purpura, or in premature infants.[44]

Methylprednisolone, like all other glucocorticoids, must be used with great caution in patients with peptic ulcer, heart disease or hypertension with heart failure, certain infectious illnesses such as varicella and tuberculosis, psychoses, diabetes, osteoporosis, or glaucoma.[45]