Dietary Conjugated Linoleic Acid‐c9t11 Prevents Collagen‐Induced Arthritis, Whereas Conjugated Linoleic Acid‐t10c12 Increases Arthritic Severity

Abstract

Two conjugated linoleic acid (CLA) isomers, cis-9, trans-11 (CLAc9t11) and trans-10, cis-12 (CLAt10c12), reduce inflammation in a number of animal models, including collagen-induced arthritis (CA). However, little is known about the ability of individual CLA isomers to prevent autoimmune disease onset. Evidence that mixed isomer CLA drives T helper cell (Th) 1 responses suggests that CLA, or a specific isomer, exacerbates onset of Th1 autoimmune diseases. In two experiments, we examined if prior dietary exposure to CLAt10c12 (experiment 1) or CLAc9t11 (experiment 2) affected the incidence or severity of CA. DBA/1 mice were fed a semi purified diet with either 6% corn oil (CO, w/w), 5.75% CO plus 0.25% CLAt10c12, or 5.5% CO plus 0.5% CLAc9t11 prior to arthritis development. Arthritis incidence and severity, anti-collagen antibodies, paw cytokines, and hepatic fatty acids were measured. CLAt10c12 had no effect on arthritis incidence but increased arthritic severity (42%, P = 0.02); however, CLAc9t11 decreased arthritis incidence 39% compared to CO fed mice (P = 0.01), but had no effect on disease severity. CLAt10c12-induced increase in anti-collagen type II IgG antibodies may be a mechanism by which this isomer increased arthritic severity, and CLAc9t11-induced increase in Th2 paw cytokines (IL-4 and IL-10, P ≤ 0.04) may explain how CLAc9t11 reduced the arthritis incidence. While both isomers are well known to reduce inflammation in arthritic mice, these new data suggest isomer differences when fed prior to autoimmune disease.

Conjugated Linoleic Acid Isomers Trans‐10, Cis‐12 and Cis‐9, Trans‐11 Prevent Collagen‐Induced Arthritis in a Direct Comparison

“…When fed at 0.5% of the diet, both CLAt10c12 and CLAc9t11 reduced the incidence of arthritis in the CA model compared to a diet containing CO as the principal fat source. In agreement with Muhlenbeck et al, mice fed 0.5% CLAc9t11 had at least a 37% decrease in incidence of arthritis compared to mice fed CO (Muhlenbeck et al, ). As CLAc9t11 is naturally abundant and can be enriched up to 6% in dairy fat (Shingfield et al, ), the practical intake of an effective preventative CLAc9t11 dose for humans should be further investigated.…”

“…CLAc9t11 has been shown to inhibit T‐cell differentiation into Th1 or Th17 cells (Draper et al, ; Jaudszus et al, ; Loscher et al, ; Turpeinen et al, ). In agreement with these reports, CLAc9t11, in a previous arthritis prevention study, potentiated the adaptive immune response toward a Th2 subset in nondeveloped mice (Muhlenbeck et al, ). Previous cytokine and antibody evidence suggests that the CLAt10c12 isomer may promote proliferation of T cells and differentiation to Th1 type responses during the induction of arthritis in the CA model (Cook et al, ; Loscher et al, ; Muhlenbeck et al, ; Yang and Cook, ).…”

“…In agreement with these reports, CLAc9t11, in a previous arthritis prevention study, potentiated the adaptive immune response toward a Th2 subset in nondeveloped mice (Muhlenbeck et al, ). Previous cytokine and antibody evidence suggests that the CLAt10c12 isomer may promote proliferation of T cells and differentiation to Th1 type responses during the induction of arthritis in the CA model (Cook et al, ; Loscher et al, ; Muhlenbeck et al, ; Yang and Cook, ). An early polarization toward a Th1 type response may be protective against the incidence of autoimmune arthritis by decreasing Th17 and γ/δ T cell differentiation and/or the respective cytokine repertoire (Chu et al, ; Manoury‐Schwartz et al, ; Matthys et al, ; Sarkar et al, ; Vermeire et al, ).…”

“…Future work would be benefited by measurement of paw cytokines along with paw fatty‐acid contents and oxylipins, ideally from the same specimen, to understand the relationship between dietary fatty‐acid changes and tissue‐specific outcomes on inflammation. The effect of reduced dietary LNA intake on reduced hepatic LNA abundance in CLA‐fed groups is possible; however, this and previous feeding trials suggest that similar dietary fat replacement with CLAc9t11 does not significantly reduce hepatic LNA over 4, 10, or 12 weeks (Huebner et al, ; Muhlenbeck et al, ).…”

“…A previous study reported by Muhlenbeck et al (2017) examined the preventative effects of the individual CLA isomers on arthritis incidence and reported a 39% decrease in incidence of mice fed CLAc9t11 compared to a CO fed control group. Isomer-specific differences between CLAc9t11 and CLAt10c12 were also suggested in this study; however, the treatment initiation point and dose differed between CLAt10c12 and CLAc9t11, preventing a direct comparison of their effects on arthritis incidence.…”