Gammalinolenic Acid, an Unsaturated Fatty Acid with Anti-Inflammatory Properties, Blocks Amplification of IL-1β Production by Human Monocytes

Abstract

Administration of gammalinolenic acid (GLA), an unsaturated fatty acid, reduces joint inflammation in patients with rheumatoid arthritis. Addition of GLA in vitro suppresses release of IL-1β from human monocytes stimulated with LPS. LPS-induced IL-1β release is followed by IL-1-induced IL-1β release, an amplification process termed autoinduction. We show here with peripheral blood monocytes from normal volunteers and from patients with rheumatoid arthritis by using IL-1R antagonist to block autoinduction and IL-1α stimulation to simulate autoinduction that ∼40% of IL-1β released from LPS-stimulated cells is attributable to autoinduction and that GLA reduces autoinduction of IL-1β while leaving the initial IL-1β response to LPS intact. Experiments with cells in which transcription and protein synthesis were blocked suggest that GLA induces a protein that reduces pro-IL-1β mRNA stability. IL-1β is important to host defense, but the amplification mechanism may be excessive in genetically predisposed patients. Thus, reduction of IL-1β autoinduction may be protective in some patients with endotoxic shock and with diseases characterized by chronic inflammation.