Phosphodiesterase inhibitors in the management of autoimmune disease.
Phophodiesterases inhibitors (PDEis) act by inhibiting the catabolism of cyclic nucleotides, cAMP and cGMP, which are ubiquitously expressed in cells of the immune system. Increased levels of cAMP and/or cGMP have been reported to decrease the activity of pro-inflammatory TH1 cells, attenuate experimental autoimmune encephalomyelitis and experimental arthritis. PDE5i like Sildenafil improves endothelial dysfunction and vascular remodelling in patients with pulmonary artery hypertension and refractory secondary Raynaud's phenomenon, with a potential to cause disease modification in the former. Studies in animal models of fibrosis suggest that these drugs have anti-fibrotic effect and may be potentially useful in conditions like scleroderma. They also have been shown to have renoprotective effect in animal models. The emerging trends make it necessary to exploit the full therapeutic potential of this class of drugs in various autoimmune diseases like rheumatoid arthritis, scleroderma, profibrotic conditions and PAH.
Shenoy
Padmanabha
P
Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India. drdpshenoy@gmail.com <drdpshenoy@gmail.com>
Agarwal
Vikas
V
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D002986:Clinical Trials as Topic; D000242:Cyclic AMP / Q000378:metabolism; D005355:Fibrosis / Q000517:prevention & control; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000276:immunology; D009389:Neovascularization, Pathologic; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D012595:Scleroderma, Systemic / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000098:blood supply / Q000187:drug effects* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors
D010726:Phosphodiesterase Inhibitors; D016212:Transforming Growth Factor beta; D000242:Cyclic AMP