gamma-linolenic-acid and Granulomatosis-with-Polyangiitis

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 interleukin-1beta (IL-1beta) from human monocytes stimulated with lipopolysaccharide (LPS). LPS-induced IL-1beta release is followed by IL-1-induced IL-1beta release, an amplification process termed "autoinduction." We show here, using IL-1alpha stimulation to simulate autoinduction, that administration of GLA to healthy volunteers and to patients with inflammatory arthritis reduces LPS-induced IL-1beta secretion mainly by reducing autoinduction of IL-1beta. GLA reduces LPS-induced pro-IL-1beta mRNA modestly and IL-la-induced pro-IL-1beta gene expression markedly. In addition to reducing amplification of IL-1beta, GLA increases the amount of IL-1 receptor antagonist (IL-1Ra) secreted from stimulated cells, thereby facilitating an increase in the secreted IL-1Ra/IL-1beta ratio. IL-1beta is important to host defense, but the amplification mechanism may be excessive in genetically predisposed individuals. Thus, reduction of IL-1beta autoinduction may be protective in some patients with endotoxic shock and with diseases characterized by chronic inflammation.

Topics: Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Psoriatic; Arthritis, Rheumatoid; Cells, Cultured; Female; gamma-Linolenic Acid; Granulomatosis with Polyangiitis; Humans; In Vitro Techniques; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Male; Middle Aged; Monocytes; Sialoglycoproteins; Sjogren's Syndrome