Carbidopa, a drug in use for management of Parkinson disease inhibits T cell activation and autoimmunity

• Published in: PloS one 2017-09, Vol.12 (9), p.e0183484-e0183484
• Main Authors: Zhu, Huabin, Lemos, Henrique, Bhatt, Brinda, Islam, Bianca N, Singh, Abhijit, Gurav, Ashish, Huang, Lei, Browning, Darren D, Mellor, Andrew, Fulzele, Sadanand, Singh, Nagendra
• Format: Article
• Language: English
• Subjects: Analysis; Animal models; Animals; Antigens; Antiparkinson Agents - pharmacology; Arthritis; Arthritis, Experimental - drug therapy; Arthritis, Experimental - immunology; Arthritis, Experimental - metabolism; Arthritis, Experimental - pathology; Autoimmune diseases; Autoimmune Diseases - immunology; Autoimmune Diseases - metabolism; Autoimmunity; Autoimmunity - drug effects; Biochemistry; Biology and Life Sciences; Brain; Carbidopa; Carbidopa - pharmacology; Cell activation; Central nervous system; Collagen; Complications and side effects; Conversion; Cytokines; Cytokines - metabolism; Dendritic cells; Disease control; Disease Models, Animal; Dopamine; Dopamine Agents - pharmacology; Dosage and administration; Drug therapy; Encephalitis; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - metabolism; Experimental allergic encephalomyelitis; Gene expression; Genetic aspects; Glycoproteins; Immune system; Immunological memory; Immunology; In vitro methods and tests; Infiltration; Inflammation; Inflammation Mediators - metabolism; Kinases; Legs; Levodopa; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Lymphocyte Count; Lymphocytes; Lymphocytes T; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Medicine; Medicine and Health Sciences; Memory cells; Mice; Molecular biology; Movement disorders; Myelin; Nervous system; Neurodegenerative diseases; Neurosciences; Oligodendrocyte-myelin glycoprotein; Organs; Parkinson disease; Parkinson's disease; Parkinsons disease; Physical Sciences; Physiological aspects; Research and Analysis Methods; Serotonin; Side effects; T cells; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Trends
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0183484

Carbidopa is a drug that blocks conversion of levodopa to dopamine outside of central nervous system (CNS) and thus inhibits unwanted side effects of levodopa on organs located outside of CNS during management of Parkinson's Disease (PD). PD is associated with increased expression of inflammatory genes in peripheral and central nervous system (CNS), infiltration of immune cells into brain, and increased numbers of activated/memory T cells. Animal models of PD have shown a critical role of T cells in inducing pathology in CNS. However, the effect of carbidopa on T cell responses in vivo is unknown. In this report, we show that carbidopa strongly inhibited T cell activation in vitro and in vivo. Accordingly, carbidopa mitigated myelin oligodendrocyte glycoprotein peptide fragment 35-55 (MOG-35-55) induced experimental autoimmune encephalitis (EAE) and collagen induced arthritis in animal models. The data presented here suggest that in addition to blocking peripheral conversion of levodopa, carbidopa may inhibit T cell responses in PD individuals and implicate a potential therapeutic use of carbidopa in suppression of T cell mediated pathologies.