Methylprednisolone is a synthetic glucocorticoid receptor agonist, used to achieve prompt suppression of inflammation.

In vitro: Methylprednisolone (2-10 mg/kg) significantly inhibited TNF production. High doses of methylprednisolone (50 mg/kg) increased LPS-induced IL-10 levels. Methylprednisolone (0.01-100 μg/ml) increased the biosynthesis of IL-10 in LPS-activated mouse peritoneal macrophages [1]. In WG patients and controls, methylprednisolone (MP) down-regulated the spontaneous and the staphylococcal enterotoxin B (SEB)-induced release of chemokines from peripheral blood mononuclear cells (PBMC)[2]. Treatment with 0.25 mM methylprednisolone inhibited acantholysis in skin cultures directly [3].

In vivo: Methylprednisolone (30 mg/kg, i.v.) given immediately after SCI reduced TNF-α expression by 55% (P<0.01) and NF-kB binding activity. Methylprednisolone suppressed the Post-traumatic inflammatory activity caused by TNF-alpha-NF-kB cascade[4]. Intravenously administration of MP (30 mg/kg) reduced the number of ED1-positive cells by 82% in the rostral cord stump and 66% in the caudal stump. In the adult rat, MP administration shortly after spinal cord transection resulted in a long-term reduction of ED1-positive cells and spinal tissue loss, reduced dieback of vestibule spinal fibres, and a transient sprouting of vestibule spinal fibres near the lesion at 1 and 2 weeks post-lesion. MP treatment also significantly reduced the tissue loss in both cord stumps at 2, 4 and 8 week post-injury[5].

Cllinical trials: In patients with acute spinal cord injury diagnosed in National Acute Spinal Cord Injury Study (NASCIS) centers within 8 hours of injury, methylprednisolone treatment for 48 hours improved motor recovery at 6 weeks (P= 0.09) and 6 months (P= 0.07) after injury[6]. In patients with acute spinal-cord injury, methylprednisolone (30 mg/kg) followed by infusion at 5.4 mg/kg/hour for 23 hours improved neurologic recovery. Among patients treated with methylprednisolone (30 mg/kg), mortality at 14 days was significantly increasedsecondary infection[7]. Methylprednisolone has entered clinical trials in patients with severe renel vasculitis and lupus nephritis.

References:
[1] Marchant A, Amraoui Z, Gueydan C, et al.  Methylprednisolone differentially regulates IL‐10 and tumour necrosis factor (TNF) production during murine endotoxaemia[J]. Clinical & Experimental Immunology, 1996, 106(1): 91-96.
[2] Torheim E A, Yndestad A, Bjerkeli V, et al.  Increased expression of chemokines in patients with Wegener's granulomatosis modulating effects of methylprednisolone in vitro[J]. Clinical & Experimental Immunology, 2005, 140(2): 376-383.
[3] Swanson D L, Dahl M V.  Methylprednisolone inhibits pemphigus acantholysis in skin cultures[J]. Journal of investigative dermatology, 1983, 81(3): 258-260.
[4] Xu J, Fan G, Chen S, et al.  Methylprednisolone inhibition of TNF-α expression and NF-kB activation after spinal cord injury in rats[J]. Molecular brain research, 1998, 59(2): 135-142.
[5] Oudega M, Vargas C G, Weber A B, et al.  [J]. European Journal of Neuroscience, 1999, 11(7): 2453-2464.Long‐ erm effects of methylprednisolone following transection of adult rat spinal cord
[6] Bracken M B, Shepard M J, Holford T R, et al.  Administration of methylprednisolone for 24 or 48 hours or tirilazadmesylate for 48 hours in the treatment of acute spinal cord injury: results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial[J]. Jama, 1997, 277(20): 1597-1604.
[7] Bracken M B, Shepard M J, Collins W F, et al.  A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury: results of the Second National Acute Spinal Cord Injury Study[J]. New England Journal of Medicine, 1990, 322(20): 1405-1411.