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Title: EVALUATION OF THE ACUTE PHASE RESPONSE IN CLONED PIGS FOLLOWING A LIPOPOLYSACCARIDE CHALLENGE

Author
item Carroll, Jeffery - Jeff Carroll
item CARTER, D. BART - UNIVERSITY OF MISSOURI
item KORTE, SCOTT - UNIVERSITY OF MISSOURI
item PRATHER, RANDALL - UNIVERSITY OF MISSOURI

Submitted to: Domestic Animal Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/9/2005
Publication Date: 10/1/2005
Citation: Carroll, J.A., Carter, D., Korte, S.W., Prather, R.S. 2005. Evaluation of the acute phase response in cloned pigs following a lipopolysaccaride challenge. Domestic Animal Endocrinology. 29(3):564-572.

Interpretive Summary: Cloning by somatic cell nuclear transfer (SCNT) is currently the leading method for the production of both transgenic and gene-knockout large animal species. Genetically modified animals have been developed that serve as bioreactors, biomedical research models, and as potential organ donors for xenotransplantation. While numerous reports have detailed that cloned animals appear normal, perinatal and early postnatal death losses still appear to be higher than in control animals. To date, these perinatal and early postnatal deaths have been attributed to a plethora of abnormalities including, but not limited to, metabolic and cardiopulmonary abnormalities, lymphoid hypoplasia, and neonatal respiratory distress. Additionally, other reports have indicated that cloned calves, lambs, goats and piglets have died of bacterial infections and sudden death of unknown cause in the neonatal period. Unfortunately, there remains a rather large void in the available information concerning the details surrounding the early deaths of cloned animals. Therefore, the objective of this study was to evaluate the innate immune response, as indicated by serum concentrations of cortisol, tumor necrosis factor-alpha (TNF-alpha), and interleukin (IL)-6, of apparently-normal, cloned piglets following a lipopolysaccharide challenge. We found that basal serum concentrations of cortisol and TNF-alpha were lower in cloned pigs as compared to control pigs. Additionally, following the lipopolysaccharide challenge, serum concentrations of cortisol, TNF-alpha and IL-6 were greater in control pigs as compared to cloned pigs. To our knowledge, this is the first study to report the cortisol, TNF-alpha and IL-6 profiles associated with the innate immune response following an endotoxin challenge in any cloned species. In and of themselves, the hormone and cytokine profiles reported herein will be a significant contribution towards our understanding, and perhaps our ability to prevent or reduce the incidence of perinatal and early postnatal deaths in cloned animals. Additionally, these results warrant further investigation of a possible adrenal cortex insufficiency, and a more indepth evaluation and testing of innate immunity in cloned animals.

Technical Abstract: The objective of the current study was to evaluate the innate immune response in cloned (n = 9) pigs as compared to genetically similar non-cloned (control; n = 11) pigs following an endotoxin challenge with lipopolysaccharide (LPS; 25 ug/kg body weight). Both groups were weaned at 21 days of age and maintained in individual pens in the same experimental room until sample collection 1 week later. Blood samples were collected at 30-min intervals for 2 hours prior to (basal) and 4 hours after the LPS challenge via a jugular catheter. Serum samples were analyzed for cortisol, tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6). Basal serum concentrations of cortisol and TNF-alpha were lower (P < 0.05) in cloned pigs as compared to control pigs. Basal serum concentration of IL-6 was undetectable in both groups of pigs. Following the LPS challenge, there was a time-by-group interaction (P < 0.0001) such that serum concentrations of cortisol, TNF-alpha, and IL-6 were greater in control pigs as compared to cloned pigs. These are the first results to demonstrate that stress hormone and proinflammatory cytokine profiles associated with the innate immune response, as well as the basal immune function, of cloned pigs are altered compared to genetically similar non-cloned pigs.