Gammalinolenic acid, an unsaturated fatty acid with anti-inflammatory properties, blocks amplification of IL-1 beta production by human monocytes.
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.
Furse
R K
RK
Department of Medicine, Division of Rheumatology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Rossetti
R G
RG
Zurier
R B
RB
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*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011498:Protein Precursors; D012333:RNA, Messenger; D017965:gamma-Linolenic Acid