Gammalinolenic acid, an unsaturated fatty acid with anti-inflammatory properties, blocks amplification of IL-1 beta production by human monocytes

• Published in: The Journal of immunology (1950) Vol. 167; no. 1; pp. 490 - 496
• Main Authors: Furse, R K, Rossetti, R G, Zurier, R B
• Format: Journal Article
• Language: English
• Published: United States 01.07.2001
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - pathology; Cell Separation; Cells, Cultured; Dose-Response Relationship, Drug; Dose-Response Relationship, Immunologic; Female; g-linolenic acid; gamma-Linolenic Acid - pharmacology; Gene Expression Regulation - drug effects; Humans; Interleukin 1^b; Interleukin-1 - antagonists & inhibitors; Interleukin-1 - biosynthesis; Interleukin-1 - metabolism; Interleukin-1 - physiology; Lipopolysaccharides - pharmacology; Macrophage Activation - drug effects; Middle Aged; Monocytes - drug effects; Monocytes - metabolism; Protein Precursors - biosynthesis; Protein Precursors - genetics; Protein Precursors - metabolism; RNA, Messenger - biosynthesis; RNA, Messenger - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.1.490

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.