Oral GABA treatment downregulates inflammatory responses in a mouse model of rheumatoid arthritis

Autoimmunity. 2011 Sep;44(6):465-70. doi: 10.3109/08916934.2011.571223. Epub 2011 May 23.


Current treatments for rheumatoid arthritis (RA) have long-term side effects such that new treatments are needed that can safely help manage the disease. There is a growing appreciation that GABA receptors (GABA-Rs) on immune cells provide new targets that can be used to modulate immune cell activity. Here, we show for the first time that activation of peripheral GABA-Rs can inhibit the development of disease in the collagen-induced arthritis (CIA) mouse model of RA. Mice that received oral GABA had a reduced incidence of CIA, and those mice that did develop CIA had milder symptoms. T cells from GABA-treated mice displayed reduced proliferative responses to collagen and their APC had a reduced ability to promote the proliferation of collagen-reactive T cells. Thus, GABA downregulated both T-cell autoimmunity and APC activity. Collagen-reactive T cells from GABA-treated mice displayed reduced recall responses in the presence of GABA ex vivo, indicating that GABA consumption did not desensitize these cells to GABA. GABA-treated mice had reduced collagen-reactive IgG2a, but not IgG1 antibodies, consistent with reduced Th1 help. The levels of serum anti-collagen IgG2a antibodies were correlated significantly with the CIA disease scores of individual mice. Our results suggest that activation of peripheral GABA-Rs may provide a new modality to modulate T cell, B cell, and APC activity and help ameliorate RA and other inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / immunology*
  • Arthritis, Rheumatoid / chemically induced
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology*
  • Collagen
  • Immunoglobulin G / blood
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred DBA
  • Receptors, GABA / immunology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • gamma-Aminobutyric Acid / administration & dosage
  • gamma-Aminobutyric Acid / therapeutic use*


  • Immunoglobulin G
  • Receptors, GABA
  • gamma-Aminobutyric Acid
  • Collagen