jour 28. Ceux du groupe lipopolysaccharides isonouris ont ete apparies par poids corporel avec les .... induce endotoxemia without causing death (16). The.
ARTICLES
Effects of immune challenge on concentrations of serum insulin-like growth factor-I and growth performance in pigs William Hevener, Patricia A. Routh, Glen W. Almond Abstract
This study was designed to determine the long-term effects of repeated endotoxin treatimmunization against human serum albumin on concentrations of serum insulin-like growth factor-I (IGF-I) and other indicators of growth performance in growing pigs. Thirty gilts (38.5 ± 0.9 kg) were randomly assigned to 5 treatment groups (n = 6 animals/group): 1) lipopolysaccharide injections, 2) lipopolysaccharide pair-fed, 3) human serum albumin immunization, 4) human serum albumin pair-fed, and 5) control. Pigs in the lipopolysaccharide group were treated intramuscularly with lipopolysaccharide on Days 0-3. The pigs in the human serum albumin group were immunized with human serum albumin emulsified in Freund's adjuvant on Day 0 and administered a booster on Day 28. The lipopolysaccharide pair-fed pigs were matched by body weight and pair-wise fed with pigs treated with lipopolysaccharide. Similarly, human serum albumin pair-fed pigs were matched to human serum albumin immunized pigs. Serum IGF-I concentrations did not differ between or within groups. There was no difference in feed disappearance between groups prior to the initiation of treatments. The lipopolysaccharide group had a decrease (P = 0.0 13) in feed disappearance on Day 0 compared with control and human serum albumin groups. On Day 1, both lipopolysaccharide and human serum albumin groups differed (P < 0.05) from control. Average daily gain and total weight gain did not differ between groups; however, feed efficiency differed (P < 0.05) between lipopolysaccharide and control groups. Long-term effects of repeated endotoxin challenge or immunization on IGF-I concentrations and growth were not evident in the present study. This failure presumably was due to the development of endotoxin tolerance and a relatively innocuous vaccination against human serum albumin. ment or
Resume - Effets d'epreuves immunologiques sur les concentrations du facteur de croissance de type insulinique-1 et le niveau de croissance des porcs. Cette etude etait destinee a determiner les effets a long terme de traitements repetes d'endotoxines ou d'immunisations contre l'albumine serique humaine sur les concentrations du facteur de croissance de type insulinique- (IGF- 1) chez des porcs en croissance. Trente cochettes (38.5 = 0.9 kg) ont ete assignees au hasard 'a 5 groupes de traitement (n = 6 animaux/groupe): 1) injections de lipopolysaccharides, 2) lipopolysaccharidesisonouris, 3) immunisations a l'albumine serique humaine, 4) albumine serique humaine insonouris et 5) temoins. Les porcs du groupe lipopolysaccharides ont ete traites par voie intramusculaire avec des lipopolysaccharides des jours 0 a 3. Les porcs de groups albumine serique humaine ont et6 immunises a l'albumine serique humaine emulsifiee dans l'adjuvent de Freund au jour 0 et en rappel au jour 28. Ceux du groupe lipopolysaccharides isonouris ont ete apparies par poids corporel avec les porcs traites aux lipopolysaccharides. De la meme fa,on, les porcs du groupe albumine serique humaine isonouris ont 6te apparies a ceux immunises 'a l'albumine serique humaine. Les concentrations de IFG-1 ne differaient pas entre les groupes ou parmi les groupes. I1 n'y avait pas de difference dans la prise alimentaire entre les divers groupes avant le debut des traitements. Le groupe lipopolysaccharides a subit une diminution de prise alimentaire (P = 0.013) au jour 0 comparativement aux groupes
College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606-1499 USA. Address correspondence and reprint requests to Dr. Glen Almond.
Materials for radioimmunoassays were provided by the National Hormone and Pituitary Program, the National Institute of Child Health and Human Development, and the United States Department of Agriculture. The results were presented in abstract form at the 3rd Conference on Farm Animal Endocrinology, Brussels, Belgium, December, 1998. 782
Can Vet J Volume 40, November 1999
temoin et albumine serique humaine. Au jour 1, les deux groupes lipopolysaccharides et albumine serique humaine diff6raient (P < 0.05) des temoins. Les moyennes des gains de poids quotidiens et totaux ne differaient pas entre les groupes; cependant, l'efficacit6 alimentaire etait differente (P < 0.05) entre les groupes lipopolysaccharides et temoin. Les effets a long terme d'epreuves repetees aux endotoxines ou d'immunisations sur les concentrations d'IGF-l et sur la croissance n'ont pas ete diff6rents dans cette etude. Cet echec est presumement du' a une tolerance aux endotoxines et 'a une vaccination relativement inoffensive contre l'albumine serique humaine. (Traduit par docteur Andre Blouin) Can Vet J 1999; 40: 782-786
Introduction mmunological stress affected weight gain and feed conversion in poultry (1) and pigs (2,3); however, the exact mechanisms that impair growth are not fully understood. It was suggested that metabolism is altered to facilitate the immune response and disease resistance rather than support growth (4). Obviously, immune stress (disease) may impair growth through reduced feed intake, but slow growth may be attributable to factors other than nutritional deficiencies (5). Serum concentrations of insulin-like growth factor-I (IGF-I) are associated with an animal's growth rate and ultimate size (6,7). Studies showed that IGF-I concentrations are influenced by feed intake and changes in metabolic demand. Feed restriction reduced IGF-I levels in cows (8) and pigs (9); changes in ambient temperature altered metabolic demand and, consequently, influenced IGF-I levels (10). So, it is reasonable to assume that a metabolic shift, associated with the onset of disease, affects IGF-I levels and, thus, may slow growth. Indeed, acute immunological stress reduced IGF-I levels for a relatively short time (1 1,12). Serum IGF-I levels are depressed after immune challenge; however, it is not clearly understood if or how this relation between immune challenge and IGF-I impairs growth in pigs. Therefore, this study was designed to evaluate changes in IGF-I concentrations and growth following repeated treatment with Escherichia coli lipopolysaccharide (LPS) or immunization against human serum albumin (HSA). The administration of LPS was previously shown to stimulate an immune response in pigs (13) and immunization against HSA effectively induced a quantifiable antibody response (14). A second objective of the study was to further evaluate the role of feed intake on IGF-I levels in immunological-challenged pigs.
Materials and methods The experimental procedures were approved by the North Carolina State University Institutional Animal Care and Use Committee. Thirty large-white crossbred gilts (38.5 ± 0.9 kg; 11 wk of age) were used in this study. Animals were housed in a curtain-sided, finishing facility and were randomly assigned to individual pens (1 m X 2 m). Each pen was equipped with a single-hole feeder and one water drinker. The average high and low temperatures during the study were 21.5°C and 18.30C, respectively. Five treatment groups (n = 6 animals/group) were utilized as follows: 1) control; 2) repeated treatment with lipopolysaccharide (LPS; E. coli endotoxin, serotype Can Vet J Volume 40, November 1999
055:B5; Sigma Chemical Co., St. Louis, Missouri, USA); 3) immunization against human serum albumin (HSA; lot 14H9319; Sigma Chemical Co.); 4) pair-fed to LPS group; and 5) pair-fed to HSA group. The day of the first LPS treatment and HSA immunization was considered Day 0 of the study. Individual animals in the LPS and HSA groups were matched by body weight to their individual pair-fed counterparts. The control, LPS, and HSA groups were allowed ad libitum feed intake. Feed disappearance was measured daily by collecting and weighing feed that was not consumed, and subtracting this value from the total amount fed to determine net feed consumption. The pair-fed pigs were then fed the same amount of feed as consumed by their respective treatment pair. The diet was a grower ration that met or exceeded National Research Council recommendations (15) and was provided by a commercial feed company. All animals were weighed at Days -1, 30, and 60. Treatments were initiated on Day 0. The LPS treatment consisted of an intramuscular injection (5 mg/kg body weight (BW)) of LPS dissolved in sterile saline. Pigs were treated at 0800 and 2000 on Days 0 and 1. The dose of LPS was increased to 10 mg/kg BW for the treatments on Days 2 and 3. This dose of LPS was chosen to induce endotoxemia without causing death (16). The HSA treatment consisted of immunizing pigs against HSA emulsified in Freund's complete adjuvant and giving a booster 1 mo later with HSA emulsified in Freund's incomplete adjuvant. Primary and booster immunizations were accomplished by subcutaneous injections with 1 mg and 0.65 mg HSA, respectively. Pair-fed groups were injected with sterile saline. Blood samples were collected by jugular venipuncture at time 0 (prior to treatment), Day 4 (day after last LPS treatment), and weekly for 8 wk. Blood samples were obtained prior to weighback of feed and subsequent refeeding. Blood was allowed to clot at room temperature prior to centrifugation to harvest serum. Serum samples were stored at -20°C until assayed. Serum IGF-I was assayed by using glycylglycine hydrochloride extraction procedures, as previously described (17), with modifications (12) that used rabbit anti-IGF-I antiserum (UB2-495) (obtained from Drs. L. Underwood and J. Van Wyk, National Hormone and Pituitary Program, University of North Carolina, Raleigh, North Carolina, USA). The standard source was recombinant human IGF-I (Amgen, Thousand Oaks, California, USA). The intra-assay coefficient of variation was 11.9%. Assay sensitivity, expressed as 90% total binding, was 35 ng/mL. Double radial immunodiffusion was used to determine the antibody response in HSA-immunized animals. 783
Table 1. Evaluation [mean,(s,)] of feed disappearance, average daily gain (ADG), total body weight gain (TBG) and feed efficiency (FE). The treatment groups included lipopolysaccharide injections (LPS), pair-fed to LPS group (LPSpr), human serum albumin immunization (HSA), and pair-fed to HSA group (HSApr). Treatment Group
Control
LPS
LPSpr
HSA
HSApr
143.8 (6) 0.98 (0.04) 54.9 (2) 2.42 (0.05) 2.81 (0.08)a 2.62 (0.05)a
148.1 (3.9) 0.94 (0.03) 52.5 (1.7) 2.56 (0.08) 3.07 (0.04)a 2.82 (0.06)a
144.4 (3.3) 0.93 (0.03) 53.2 (1.7) 2.47 (0.04) 2.94 (0.03) 2.72 (0.03)
145.8 (6.6) 0.94 (0.05) 52.5 (3) 2.53 (0.08) 3.03 (0.11) 2.79 (0.08)
138 (3.6) 0.92 (0.02) 52.4 (1) 2.46 (0.04) 2.82 (0.14) 2.64 (0.08)
Parameter Feed disappearance (Total; kg) ADG (kg) TBG (kg) FE (1st month) FE (2nd month) FE Overall
aPlanned multiple comparisons of FE means were made by least significant differences and CON and LPS groups differed at P
