Suppression of leukotriene B4 generation by ex-vivo neutrophils isolated from asthma patients on dietary supplementation with gammalinolenic acid-containing borage oil: possible implication in asthma.
Dietary gammalinolenic acid (GLA), a potent inhibitor of 5-lipoxygenase (5-LOX) and suppressor of leukotriene B4 (LTB4), can attenuate the clinical course of rheumatoid arthritics, with negligible side effects. Since Zileuton, also an inhibitor of 5-LOX, attenuates asthma but with an undesirable side effect, we investigated whether dietary GLA would suppress biosynthesis of PMN-LTB4 isolated from asthma patients and attenuate asthma. Twenty-four mild-moderate asthma patients (16-75 years) were randomized to receive either 2.0 g daily GLA (borage oil) or corn oil (placebo) for 12 months. Blood drawn at 3 months intervals was used to prepare sera for fatty acid analysis, PMNs for determining phospholipid fatty acids and for LTB4 generation. Patients were monitored by daily asthma scores, pulmonary function, and exhaled NO. Ingestion of daily GLA (i) increased DGLA (GLA metabolite) in PMN-phospholipids; (ii) increased generation of PMN-15-HETrE (5-LOX metabolite of DGLA). Increased PMN-DGLA/15-HETrE paralleled the decreased PMN generation of proinflammatory LTB4. However, the suppression of PMN-LTB4 did not reveal statistically significant suppression of the asthma scores evaluated. Nonetheless, the study demonstrated dietary fatty acid modulation of endogenous inflammatory mediators without side effects and thus warrant further explorations into the roles of GLA at higher doses, leukotrienes and asthma.
Ziboh
Vincent A
VA
Division of Rheumatology, Allergy and Clinical Immunology, Department of Dermatology, University of California at Davis School of Medicine, TB 192, Davis, CA 95616, USA.
Naguwa
Stanley
S
Vang
Kao
K
Wineinger
Julie
J
Morrissey
Brian M
BM
Watnik
Mitchell
M
Gershwin
M Eric
ME
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000628:therapy; D001249:Asthma / Q000097:blood / Q000628:therapy*; D019587:Dietary Supplements; D004311:Double-Blind Method; D005227:Fatty Acids / Q000032:analysis / Q000097:blood; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007975:Leukotriene B4 / Q000096:biosynthesis*; D016859:Lipoxygenase Inhibitors; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D010938:Plant Oils / Q000008:administration & dosage* / Q000032:analysis; D011446:Prospective Studies; D017965:gamma-Linolenic Acid / Q000008:administration & dosage*
D005227:Fatty Acids; D016859:Lipoxygenase Inhibitors; D010938:Plant Oils; D007975:Leukotriene B4; D017965:gamma-Linolenic Acid; C079363:borage oil; C063449:zileuton; D006918:Hydroxyurea