title: Oral administration of gammalinolenic acid, an unsaturated fatty acid with anti-inflammatory properties, modulates interleukin-1beta 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 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.
authors: University of Massachusetts Medical School, Department of Medicine, Worcester 01655, USA.
authors: Robert K
authors: RK
authors: Furse
authors: Ronald G
authors: RG
authors: Rossetti
authors: Christina M
authors: CM
authors: Seiler
authors: Robert B
authors: RB
authors: Zurier
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D015535:Arthritis, Psoriatic / Q000188:drug therapy / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000096:biosynthesis*; D012859:Sjogren's Syndrome / Q000188:drug therapy / Q000378:metabolism; D017965:gamma-Linolenic Acid / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D017965:gamma-Linolenic Acid