Omega-3 fatty acids suppress the enhanced production of 5-lipoxygenase products from polymorph neutrophil granulocytes in cystic fibrosis.
Pulmonary damage in cystic br osis (CF) is associated with chronic inflammation mediated in part by proinflammatory 5-lipoxygenase products (5-LOP, leukotrienes and 5-hydroxyeicosatetraenoic acid) from polymorph neutrophil granulocytes (PMN). The authors studied 5-LOP formation of PMN from CF patients and in vitro effects of added eicosapentaenoic acid (EPA) and fish oil. Circulating PMN were isolated from 10 CF patients without acute infections and 10 control persons of the same age (4-20 years). Total 5-LOP liberation from PMN of CF patients was significantly increased over controls after incubation with the calcium ionophore A23 (1 mumol L-1) without arachidonic acid (AA) (380 +/- 24 vs. 294 +/- 28 pmol mL-1) and with 10 mumol L-1 AA (1303 +/- 104 vs. 1015 +/- 104 pmol mL-1), and there were nonsignificant trends to high values after incubation with 5 mumol L-1 platelet activating factor (PAF, 134% of controls) and 1 mumol L-1 formyl-methionylleucyl-phenylalanine (FMLP, 125%). The addition of 100 micrograms mL-1 fish oil to PMN of CF patients challenged with A23 completely suppressed synthesis of proinflammatory 5-LOP of the 4-series, while inactive 5-LOP metabolites of the 5-series were produced. Added EPA (10 mumol L-1) also suppressed 4-series 5-LOP and significantly reduced leukotriene B4 concentration by 48% from 39.9 +/- 3.2 to 20.6 +/- 11.4 pmol L-1, again with a concomittant increase of inactive 5-series metabolites. The authors conclude that the turnover of endogenous and exogenous AA is enhanced in CF, possibly due to stimulated phospholipase A2 activity. The relatively small effect of the receptor dependent stimuli PAF and FMLP may be caused by a down-regulation of PMN receptors in CF. Supplementation of long-chain omega-3-fatty acids may be beneficial for reducing excessive inflammation in CF patients and should be further evaluated.
Keicher
U
U
Kinderpoliklinik, Ludwig-Maximilians-Universität, Munich, Germany.
Koletzko
B
B
Reinhardt
D
D
D000293:Adolescent; D000328:Adult; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D001095:Arachidonic Acids / Q000378:metabolism*; D002396:Catechols / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000097:blood*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005395:Fish Oils / Q000494:pharmacology; D006801:Humans; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D020032:Tyrphostins
D001095:Arachidonic Acids; D002396:Catechols; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D015289:Leukotrienes; D009570:Nitriles; D010972:Platelet Activating Factor; D020032:Tyrphostins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015118:Eicosapentaenoic Acid; D001094:Arachidonate 5-Lipoxygenase; C060641:tyrphostin A23