Dietary Conjugated Linoleic Acid Decreased Cachexia, Macrophage Tumor Necrosis Factor-α Production, and Modifies Splenocyte Cytokines Production¹

Abstract

The effect of conjugated linoleic acid (CLA) on macrophage functions were studied in vitro, in vivo, and ex vivo. In RAW macrophage cell line, CLA (mixed isomers) was shown to inhibit lipopolysaccharide (LPS)-stimulated tumor necrosis factor-alpha (TNF-alpha) production. Two CLA isomers, c9,t11 and t10,c12, were tested on RAW cells and it was found that the c9,t11 was the isomer responsible for the inhibition of LPS-induced TNF-alpha production. BALB/c mice were used to determine the effect of dietary CLA on body weight wasting and feed intake after LPS injection. CLA was protective against LPS-induced body weight wasting and anorexia. Plasma TNF-alpha levels after LPS injection were lower in the CLA group compared with the corn oil-fed control group 2 hr post-LPS injection. In a separate experiment, 30 mice were fed a CLA-supplemented diet or a corn oil-supplemented diet for 6 weeks and peritoneal resident macrophages were obtained for measuring TNF-alpha and nitric oxide production after in vitro exposure to interferon-gamma (IFN-gamma) and/or LPS. TNF-alpha production was not found to be different in peritoneal macrophages from mice fed the dietary treatments, but less nitric oxide was produced in macrophages from CLA-fed mice upon stimulation when compared with macrophages from control-fed mice. Splenocytes were also collected from the mice fed the dietary treatments and stimulated to produce cytokines in culture. Supernatant was used to run cytokine enzyme-linked immunoabsorbant assays. Interleukin-4 (IL-4) was decreased in CLA-fed mice when splenocytes were stimulated with concanavalin A (Con A) for 44 hr; however, IL-2 and the IL-2-to-IL-4 ratio were elevated.

The effects of conjugated linoleic acid supplementation on immune function in healthy volunteers

“…In the study of Kelley et al (2002) both the c9,t11-CLA and t10,c12-CLA significantly enhanced LPS-stimulated TNFa secretion in C57BL/6 mice, while Yamasaki et al (2003) reported a significant increase in Con A-induced TNFa production following dietary supplementation with the c9,t11-CLA alone. In contrast, in vitro studies with Raw264.7 macrophages showed that the c9,t11-CLA was associated with a dose-dependent decrease in LPS-induced TNFa production, with smaller decreases associated with the t10,c12-CLA isomer and a CLA isomeric mix (Yang & Cook, 2003). Recent human studies demonstrate that supplementation with CLA blends had no significant effect on ex vivo PHA-induced IL-2 secretion or LPS-stimulated TNFa production (Kelley et al, 2000(Kelley et al, , 2001Albers et al, 2003).…”

“…Three animal feeding trials showed that CLA isomeric blends significantly increased Con A-and PHA-induced IL-2 production in mice Hayek et al, 1999;Yang & Cook, 2003), whereas two studies reported no effect (Kelley et al, 2002;Yamasaki et al, 2003). Indeed, Kelley et al (2002) showed that feeding C57Bl/6N mice diets enriched with the purified c9,t11-CLA or t10,c12-CLA did not affect Con A-stimulated IL-2 production.…”

“…TNFa is a potent proinflammatory cytokine that induces activation of monocytes and macrophages, and other proinflammatory cytokines (Tracey & Cerami, 1994;Hillman & Haas, 1995). Dietary supplementation with CLA blends decreased plasma TNFa concentrations and basal macrophage TNFa production but had no effect on LPS-induced TNFa secretion in rat or murine macrophages (Turek et al, 1998;Yang & Cook, 2003). Conversely, studies investigating the effects of the purified isomers have yielded equivocal results.…”

“…CLA blends are also reported to depress macrophage phagocytosis (Cook et al, 1993;Miller et al, 1994) and to modulate eicosanoid production, particularly prostaglandin E 2 (PGE 2 ) Kavanaugh et al, 1999). In addition, CLA isomeric blends enhanced IL-2 production in mice Hayek et al, 1999;Yang & Cook, 2003), but reduced IL-4, IL-6 and tumor necrosis factor a (TNFa) production in BALB/c mice and in Sprague-Dawley rats (Turek et al, 1998;Yang & Cook, 2003). Most of the above studies used CLA isomeric blends.…”

Obtención de leche bovina reducida en grasa saturada y naturalmente enriquecida en ácido linoleico conjugado

“…El consumo de lácteos estándar no permitiría alcanzar la ingestión diaria de CLA necesaria para la expresión de sus potenciales efectos preventivos de patologías cardiovasculares (Bhattacharya, et al, 2006), diabetes (Ryder, et al, 2001;Houseknecht, 1998), aterosclerosis (Lee, et al, 1994), cáncer (Ha, et al, 1990;Ip, et al, 1999), hipertensión (Bhattacharya, et al, 2006) y obesidad (Watkins y Li, 2003;Bhattacharya, et al, 2006). También se describen efectos antiinflamatorios del CLA (Yang y Cook, 2003;Miller, et al, 1994).…”