Evaluation of chronic immune system stimulation models in growing pigs

Abstract

Two experiments (EXPs) were conducted to evaluate models of immune system stimulation (ISS) that can be used in nutrient metabolism studies in growing pigs. In EXP I, the pig's immune response to three non-pathogenic immunogens was evaluated, whereas in EXP II the pig's more general response to one of the immunogens was contrasted with observations on non-ISS pigs. In EXP I, nine growing barrows were fitted with a jugular catheter, and after recovery assigned to one of three treatments. Three immunogens were tested during a 10-day ISS period: (i) repeated injection of increasing amounts of Escherichia coli lipopolysaccharide (LPS); (ii) repeated subcutaneous injection of turpentine (TURP); and (iii) feeding grains naturally contaminated with mycotoxins (MYCO). In EXP II, 36 growing barrows were injected repeatedly with either saline (n 5 12) or increasing amounts of LPS (n 5 24) for 7 days (initial dose 60 mg/kg body weight). Treating pigs with TURP and LPS reduced feed intake (P , 0.02), whereas feed intake was not reduced in pigs on MYCO. Average daily gain (ADG; kg/day) of pigs on LPS (0.50) was higher than that of pigs on TURP (0.19), but lower than that of pigs on MYCO (0.61; P , 0.01). Body temperature was elevated in pigs on LPS and TURP, by 0.88C and 0.78C, respectively, relative to pre-ISS challenge values (39.38C; P , 0.02), but remained unchanged in pigs on MYCO. Plasma concentrations of interleukin-1b were increased in pigs treated with LPS and TURP (56% and 55%, respectively, relative to 22.3 pg/ml for pre-ISS; P , 0.01), but not in MYCO-treated pigs. Plasma cortisol concentrations remained unchanged for pigs on MYCO and TURP, but were reduced in LPS-treated pigs (30% relative to 29.8 ng/ml for pre-ISS; P , 0.05). Red blood cell glutathione concentrations were lower in TURP-treated pigs (13% relative to 1.38 mM for pre-ISS; P , 0.05), but were unaffected in pigs on LPS and MYCO. In EXP I, TURP caused severe responses including skin ulceration and substantial reductions in feed intake and ADG, whereas MYCO did not induce effective ISS. In EXP II, ISS increased relative organ weights, eye temperature, white blood cell count and plasma acute-phase proteins (P , 0.05), confirming that repeated injection with increasing amounts of LPS induced chronic and relatively mild ISS. Repeated injection with increasing amounts of LPS is a suitable model for studying nutrient metabolism and evaluating the efficacy of nutritional intervention during chronic ISS in growing pigs.

Vitamin E and omega-3 fatty acids independently attenuate plasma concentrations of proinflammatory cytokines and prostaglandin E2 in Escherichia coli lipopolysaccharide-challenged growing–finishing pigs1

“…Interestingly, there was a strong negative correlation between TNF-α and IL-1β concentrations in serum, indicating that LPS-induced immune system stimulation may primarily activate TNF-α rather than IL-1β. However, previous studies showed increased production of both TNF-α and IL-1β after LPS challenge in pigs (Wright et al, 2000;Rakhshandeh and de Lange, 2012). The serotype of E. coli LPS, sampling timing, and dose rate of LPS might have influenced serum concentrations of cytokines and immunity-related molecules, as the response of pigs to LPS was reported to be dose dependent (Webel et al, 1997).…”

“…Disease challenge, whether it is clinical or subclinical, under commercial conditions of pig production can lead to the production of numerous immune system-related compounds such as acute phase proteins (Wright et al, 2000) and cytokines (Curfs et al, 1997;Paradis et al, 2012;Rakhshandeh and de Lange, 2012;Rakhshandeh et al, 2014). The increased release of proinflammatory cytokines in immune system-challenged pigs causes reduced feed intake and growth performance and deterioration in feed efficiency, mainly due to altered nutrient partitioning and neurological infection responses such as anorexia and fever (Webel et al, 1997;Kim et al, 2013).…”

“…The increased release of proinflammatory cytokines in immune system-challenged pigs causes reduced feed intake and growth performance and deterioration in feed efficiency, mainly due to altered nutrient partitioning and neurological infection responses such as anorexia and fever (Webel et al, 1997;Kim et al, 2013). In the current study, E. coli LPS was chosen to mimic immune system stimulation in pigs kept under commercial conditions (Rakhshandeh and de Lange, 2012) to evaluate the dietary effects of Vit E and n-3 fatty acids in mitigating the pigs' responses to immune system stimulation and to examine effects on production and carcass composition. Escherichia coli LPS is a component of the outer membrane of E. coli and has been reported to cause fever (Johnson and von Borell, 1994;Leininger et al, 2000) and anorexia 2 25% replacement of tallow to linseed oil as a source of omega-3 fatty acid.…”

“…The serotype of E. coli LPS, sampling timing, and dose rate of LPS might have influenced serum concentrations of cytokines and immunity-related molecules, as the response of pigs to LPS was reported to be dose dependent (Webel et al, 1997). For example, Wright et al (2000) and Rakhshandeh and de Lange (2012) used LPS extracted from E. coli B55:B5 and used either 100 μg/kg via intraperitoneal injection or 60 μg/kg via intramuscular injection, whereas our study used LPS extracted from E. coli O111:B5 and 30 μg/kg via intramuscular injection. In addition, and from a continuous blood sampling study, Wright et al (2000) showed that a single dose of LPS induced an immune response for only a short period of time (i.e., less than 24 h).…”

“…The diets were formulated to meet or exceed NRC (2012) recommendations for all nutrients (Table 1). To mimic the chronic immune system stimulation typically seen in commercially housed pigs (Pastorelli et al, 2012), all pigs were challenged with an intramuscular injection of Escherichia coli lipopolysaccharide (LPs; O111:B4; Sigma-Aldrich, St. Louis, MO) twice weekly over the 6-wk experiment (Rakhshandeh and de Lange, 2012). The LPS dose rate was 30 μg/kg BW at the first injection and was increased by 15% in each subsequent injection to counteract the development of any possible resistance to the LPS.…”