Pro-inflammatory cytokine-induced SAPK/MAPK and JAK/STAT in rheumatoid arthritis and the new anti-depression drugs.
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.


CONCLUSIONS
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.
Malemud
Charles J
CJ
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
Miller
Andrew H
AH
D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy*; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000378:metabolism*
D000928:Antidepressive Agents; D050791:STAT Transcription Factors; D053612:Janus Kinases; D020928:Mitogen-Activated Protein Kinases