Charles J Malemud1, Andrew H Miller. 1. Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Department of Medicine, Division of Rheumatic Diseases, 2061 Cornell Road, Cleveland, Ohio 44106-5076, USA. cjm4@cwru.edu
Abstract
BACKGROUND: Adult rheumatoid arthritis (RA) patients are frequently clinically depressed. Peripheral inflammation in RA may influence neurotransmitter metabolism, neuroendocrine function, synaptic plasticity, as well as growth factor production, which can modify neural circuitry and contribute to depression. OBJECTIVE: A convergence between pro-inflammatory cytokine-induced synovial joint inflammation in RA and the effects of pro-inflammatory cytokines on the brain may occur through activation of the stress-activated/mitogen-activated protein kinases (SAPK/MAPK) and/or Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways. METHODS: The PubMed and Medlines databases were critically evaluated for evidence of SAPK/MAPK and/or JAK/STAT pathway activation in RA and depression. RESULTS/ CONCLUSION: Some novel anti-depression drugs that were employed in animal models of 'sickness behavior' and in human depression clinical trials suppressed clinical markers of inflammation, as well as SAPK/MAPK and/or JAK/STAT signaling in vitro. Modifying pro-inflammatory cytokine signaling pathways in the brain with antidepressants may also be useful in ameliorating peripheral inflammation in RA.
BACKGROUND: Adult rheumatoid arthritis (RA) patients are frequently clinically depressed. Peripheral inflammation in RA may influence neurotransmitter metabolism, neuroendocrine function, synaptic plasticity, as well as growth factor production, which can modify neural circuitry and contribute to depression. OBJECTIVE: A convergence between pro-inflammatory cytokine-induced synovial joint inflammation in RA and the effects of pro-inflammatory cytokines on the brain may occur through activation of the stress-activated/mitogen-activated protein kinases (SAPK/MAPK) and/or Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways. METHODS: The PubMed and Medlines databases were critically evaluated for evidence of SAPK/MAPK and/or JAK/STAT pathway activation in RA and depression. RESULTS/ CONCLUSION: Some novel anti-depression drugs that were employed in animal models of 'sickness behavior' and in humandepression clinical trials suppressed clinical markers of inflammation, as well as SAPK/MAPK and/or JAK/STAT signaling in vitro. Modifying pro-inflammatory cytokine signaling pathways in the brain with antidepressants may also be useful in ameliorating peripheral inflammation in RA.
Authors: Li Li; Lori J Silveira; Nabeel Hamzeh; May Gillespie; Peggy M Mroz; Annyce S Mayer; Tasha E Fingerlin; Lisa A Maier Journal: Eur Respir J Date: 2016-04-21 Impact factor: 16.671
Authors: Arabinda Das; M Kelly Guyton; Amena Smith; Gerald Wallace; Misty L McDowell; Denise D Matzelle; Swapan K Ray; Naren L Banik Journal: J Neurochem Date: 2012-11-22 Impact factor: 5.372