Cis-9, trans-11-Conjugated Linoleic Acid Inhibits Allergic Sensitization and Airway Inflammation via a PPAR γ-Related Mechanism in Mice3

Abstract

Milk consumption from early childhood on has been found to be inversely correlated with allergic sensitization and the onset of bronchial asthma. We tested whether cis-9,trans-11-conjugated linoleic acid (c9,t11-CLA), naturally occurring in milk fat, may prevent allergic sensitization and inhibit airway inflammation in a murine asthma model. BALB/c mice were fed a diet enriched in 1 wt% of c9,t11-CLA or a control diet 7 d prior to and for 32 d during sensitization [d 1 and 14, 100 mg/L ovalbumin (OVA) in adjuvant vs. PBS] and airway challenges (d 28-30, 1% OVA in PBS vs. PBS). Subgroups of mice were coadministered 20 micromol/L of the selective PPARgamma antagonist GW9662 during each OVA challenge. C9,t11-CLA feeding resulted in significantly reduced IgE production and allergen-induced in vivo airway hyperresponsiveness. Further, less mucous plugging of segmental bronchi and significantly reduced interleukin-5 and eosinophils were determined in bronchoalveolar lavage fluids of c9,t11-CLA-fed mice. C9,t11-CLA feeding prevented the downregulation of PPARgamma mRNA in the lung tissues observed after allergen sensitization and airway challenges in control mice. The inhibitory effects of c9,t11-CLA on airway inflammation were partially prevented by coadministration of GW9962. Further, c9,t11-CLA feeding resulted in a significantly lower concentration of the eicosanoid precursor, arachidonic acid, in tissue lipids. These findings demonstrate that dietary c9,t11-CLA can reduce allergic airway inflammation, most likely via a PPARgamma-related mechanism and by reducing eicosanoid precursors. They give new insights into the fatty acid-mediated mechanism of immunomodulation and may represent a step toward an attractive novel strategy in the dietary prevention and treatment of allergic asthma.

Bioavailability and Allergoprotective Capacity of Milk-Associated Conjugated Linoleic Acid in a Murine Model of Allergic Airway Inflammation

“…In contrast to our results, Whigham et al [42] observed a decrease in inflammatory eicosanoid mediators in comparison to the basal release of eicosanoids in CLA-supplemented animals when respiratory organs were challenged with OVA ex vivo. Furthermore, Jaudszus et al [18] showed that dietary CLA supplementation of mice with a synthetic FA affects sensitization and is capable of reducing the release of the proinflammatory cytokine IL-5. Our experiments, applying CLA in a natural matrix revealed no decrease in T H 2 cytokines in milk diet-fed animals.…”

“…Another placebo-controlled study conducted in allergic patients revealed that oral CLA supplementation improved symptoms and immunological parameters during pollen season [17]. In line with these findings an experimental approach in a murine model of asthma where mice were fed a synthetically produced CLA derivate underlined that dietary CLA uptake might lead to allergoprotection [18]. …”

Dietary <i>Trans</i> Fatty Acids Suppress the Development of Spontaneous Atopic-Like Dermatitis in NC/Nga Mice

“…Although cis-9, trans-11-conjugated linoleic is not contained in the experimental diet used in this study, it has been reported that cis-9, trans-11-conjugated linoleic exerts anti-inflammatory effects in vivo. A recent study by Jaudszus et al shows that cis-9, trans-11-conjugated linoleic acid reduces IgE production and allergen-induced airway hyperresponsiveness (12). Furthermore, bovine milk fat enriched in cis-9, trans-11-conjugated linoleic also reduces circulating allergen-specific IgE and IgG1 levels in OVA-immunized C57BL/6 mice (13).…”

Anti-allergic effect of the naturally-occurring conjugated linolenic acid isomer, jacaric acid, on the activated human mast cell line-1

“…To the best of our knowledge, this is the first study demonstrating the in vitro anti-allergic effect of CLNAs on HMC-1 cells, and this is in line with earlier findings showing that CFAs, such as CLAs, may possess anti-allergic activities. For example, Jaudszus et al (24) reported that 9Z, 11E-CLA could inhibit allergic sensitization and airway inflammation through peroxisome proliferator-activated receptor-γ dependent mechanism in mice, whereas others demonstrated that human healthy volunteers supplemented with 9Z, 11E-CLA resulted in a decreased plasma IgE level and reduced secretion of IL-5 by PBMCs (25,26). Despite these earlier findings, the underlying action mechanisms for the anti-allergic effects of CFAs, such as CLAs and CLNAs, remain poorly understood and further studies are required to elucidate the mechanisms, in vitro and in vivo, for the anti-allergic activity of CFAs.…”