title: Gammalinolenic acid, an unsaturated fatty acid with anti-inflammatory properties, blocks amplification of IL-1 beta 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-1beta from human monocytes stimulated with LPS. LPS-induced IL-1beta release is followed by IL-1-induced IL-1beta 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-1alpha stimulation to simulate autoinduction that approximately 40% of IL-1beta released from LPS-stimulated cells is attributable to autoinduction and that GLA reduces autoinduction of IL-1beta while leaving the initial IL-1beta 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-1beta mRNA stability. IL-1beta is important to host defense, but the amplification mechanism may be excessive in genetically predisposed patients. Thus, reduction of IL-1beta autoinduction may be protective in some patients with endotoxic shock and with diseases characterized by chronic inflammation.
authors: Department of Medicine, Division of Rheumatology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors: R K
authors: RK
authors: Furse
authors: R G
authors: RG
authors: Rossetti
authors: R B
authors: RB
authors: Zurier
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002469:Cell Separation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D017965:gamma-Linolenic Acid / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011498:Protein Precursors; D012333:RNA, Messenger; D017965:gamma-Linolenic Acid