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.

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.