Modulation Of Conjugated Linoleic Acid On Immunological Stress Of Weaned Pigs

Two animal feeding experiments and one in vitro experiment were conducted to investigate the immunomodulation and action mechanism of conjugated linoleic acid (CLA) on immune function of pigs in immunological stress. (1) To explore the effects of CLA on growth and immune response in early weaned pigs and the optimal dose of dietary CLA, 72 cross-bred pigs weaned at age of 23 ± 2 d were randomly allotted to feed one of four diets containing 0, 1, 2, or 3% CLA for 28 days. There were six replicates per treatment with three pigs each pen. With increased dietary CLA, average daily gain and average daily feed intake were increased quadratically (P < 0.05) and feed efficiency was increased linearly (P < 0.05); Specific ovalbumin antibody was increased quadratically (P < 0.05), and lymphocyte proliferation was enhanced linearly (P < 0.05). For improving growth and enhancing immune response, 2% CLA is optimal in weaned pigs. (2) An immunological stress model was establish through intraperitoneal injecting with E. coli lipopolysaccharide (LPS) to further evaluate the effects of CLA on growth-depression induced by immune challenge and immune response of pigs in immunological stress. 72 weaned pigs at 28 ± 2 d of age were used in a 2 2 factorial design. The main factors consisted of diets (2% CLA or 2% soybean oil) and immunological challenge (LPS or saline). On d 14 and 21, half of pigs in each dietary treatment were injected intraperitoneally with either 100 ug/kg BW LPS or an equivalent amount of sterile saline. Blood samples were collected at 3 and 24 h post-injection and lymphocytes were cultured to extract nuclear protein on d 21. Pigs were killed at 3 h post-challenge on d 29. Spleen and thymus were removed immediately for total RNA extraction to determine the mRNA relative contents of proinflammatory cytokines and peroxisome proliferator-activated receptor- (PPARy). CLA prevented the growth-suppression due to LPS challenge and improved feed efficiency (P < 0.05); CLA increased lymphocyte proliferation and percentage of CD8⁺ lymphocyte subsets (P < 0.01) and decreased the ratio of CD4+/CD8+ (P < 0.05) at 24 h post-injection. However, CLA decreased (P < 0.05) the production of plasma interleukin-6 (IL-6), tumour necrosis factor-a (TNF-a), acute phase protein (a-AGP) and PGE₂ induced by LPS challenge; CLA dereased the mRNA abundance of IL-1, IL-6 and TNF-a in spleen and thymus, while increased the mRNA abundance and activation of PPARy and the content of 15d-PGJ2 (P < 0.05). The results indicated that CLA alleviating growth depression after immune challenge is not dependent on suppressing immune system reactivity, but modulating the pro-inflammatory cytokines production at molecular level via regulating the PPARy expression and activation. (3) In order to determine the effects of two CLA isomers on anti-immunological stress and regulating immune response, peripheral blood lymphocytes of weaned pigs were cultured with media containing various concentrations (0, 50, 100, 150 and 200 umol/L) of c9, til-CLA, t10, cl2-CLA or CLA mixture, with linoleic acid (LA) as control, to investigate the effect of CLA isomers on peripheral blood lymphocyte proliferation. In addition, lymphocytes were cultured with media containing 100 umol/L fatty acids as described above and nuclear protein and total RNA were extracted to test PPARy activation and the mRNA relative contents of IL-lp\ IL-6, TNF andPPAR. Results suggested that c9, tll-CLA and tlO, cl2-CLA enhanced lymphocyte proliferation at low concentration, while inhibited lymphocyte proliferation at high concentration. Two CLA isomers suppressed the production and mRNA expression of IL-l\ IL-6 and TNF-a, whereas enhanced the activation and gene expression of PPARy in lymphocyte. The effects of t10, C12-CLA isomer on modulation of lymphocyte proliferation and inhibiting the mRNA expression of proinflammatory cytokines were greater than those of c9, t11-CLA isomer. Moreover, c9, tll-CLA and tlO, C12-CLA regulates immune function of lymphocyte in weaned pigs by modulating the PPARy act...