Font Size: a A A

Inhibition of lipid mediators in type I (immediate) hypersensitivity immune reactions by conjugated linoleic acid (CLA)

Posted on:2001-12-10Degree:Ph.DType:Thesis
University:The University of Wisconsin - MadisonCandidate:Whigham, Leah DawnFull Text:PDF
GTID:2461390014953581Subject:Health Sciences
Abstract/Summary:
Conjugated linoleic acid (CLA), a group of naturally occurring fatty acids in meat and dairy products, is structurally similar to linoleic acid except the double bonds are in a conjugated diene formation. This structural difference changes the shape of the molecule, and therefore its biological activity, including its effect on immune responses.; Because CLA had been previously shown to enhance immune reactions, we hypothesized that dietary CLA would exacerbate type I hypersensitivity reactions (allergies). We tested our hypothesis using a standard model of type I hypersensitivity, antigen sensitized guinea pigs. Guinea pigs were fed a control or CLA-supplemented diet for 2 weeks prior to and during sensitization to ovalbumin. Following feeding and sensitization, animals were euthanized and tracheae were removed for superfusion studies. Contrary to our hypothesis, dietary CLA had no effect on tracheal contractions and decreased histamine and prostaglandin E 2 (PGE2) released from tracheae in response to antigen challenge.; Due to similarity in structure between CLA and linoleic acid, and the fact that linoleic acid is the precursor of prostanoids such as PGE2 , we pursued the effect of CLA on production of prostanoids and other lipid-derived mediators. We developed a liquid chromatography/tandem mass spectrometry method to analyze the entire profile of lipid-derived mediators from a single aqueous sample. Using this method and the same feeding and sensitization protocol described above, we studied the mediator release of guinea pig trachea, lung, and bladder at basal levels and in response to antigen challenge. In these tissues, dietary CLA significantly reduced release of all prostanoids (except for PGE2 in lung and PGF2alpha in bladder, which approached significance) and cysteinyl leukotrienes (LTC4, D4 and E4) in response to antigen challenge, but had no effect on basal release.; These mediators play a large role in type I hypersensitivity responses such as allergic asthma, allergic rhinitis, and non-infectious interstitial cystitis. The finding that basal levels were not affected indicates CLA has no negative effect on the protective role some prostanoids play under non-inflammatory conditions. In conclusion, dietary CLA, previously shown to enhance immune responses, does not exacerbated type I hypersensitivity, and down-regulates antigen- induced mediator release.
Keywords/Search Tags:CLA, Linoleic acid, Hypersensitivity, Type, Immune, Conjugated, Mediators, Reactions
Related items