PMID- 38189595 OWN - NLM STAT- MEDLINE DCOM- 20240119 LR - 20240131 IS - 1525-3163 (Electronic) IS - 0021-8812 (Print) IS - 0021-8812 (Linking) VI - 102 DP - 2024 Jan 3 TI - The effect of chronic, non-pathogenic maternal immune activation on offspring postnatal muscle and immune outcomes. LID - 10.1093/jas/skad424 [doi] LID - skad424 AB - The objective was to determine the effects of maternal inflammation on offspring muscle development and postnatal innate immune response. Sixteen first-parity gilts were randomly allotted to repeated intravenous injections with lipopolysaccharide (LPS; n = 8, treatment code INFLAM) or comparable volume of phosphate buffered saline (CON, n = 8). Injections took place every other day from gestational day (GD) 70 to GD 84 with an initial dose of 10 mug LPS/kg body weight (BW) increasing by 12% each time to prevent endotoxin tolerance. On GD 70, 76, and 84, blood was collected at 0 and 4 h postinjection via jugular or ear venipuncture to determine tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1beta concentrations. After farrowing, litter mortality was recorded, and the pig closest to litter BW average was used for dissection and muscle fiber characterization. On weaning (postnatal day [PND] 21), pigs were weighed individually and 2 barrows closest to litter BW average were selected for another study. The third barrow closest to litter BW average was selected for the postnatal LPS challenge. On PND 52, pigs were given 5 mug LPS/kg BW via intraperitoneal injection, and blood was collected at 0, 4, and 8 h postinjection to determine TNF-alpha concentration. INFLAM gilt TNF-alpha concentration increased (P < 0.01) 4 h postinjection compared to 0 h postinjection, while CON gilt TNF-alpha concentration did not differ between time points. INFLAM gilt IL-6 and IL-1beta concentrations increased (P = 0.03) 4 h postinjection compared to 0 h postinjection on GD 70, but did not differ between time points on GD 76 and 84. There were no differences between INFLAM and CON gilts litter mortality outcomes (P >/= 0.13), but INFLAM pigs were smaller (P = 0.04) at birth and tended (P = 0.09) to be smaller at weaning. Muscle and organ weights did not differ (P >/= 0.17) between treatments, with the exception of semitendinosus, which was smaller (P < 0.01) in INFLAM pigs. INFLAM pigs tended (P = 0.06) to have larger type I fibers. INFLAM pig TNF-alpha concentration did not differ across time, while CON pig TNF-alpha concentration peaked (P = 0.01) 4 h postinjection. TNF-alpha concentration did not differ between treatments at 0 and 8 h postinjection, but CON pigs had increased (P = 0.01) TNF-alpha compared to INFLAM pigs 4 h postinjection. Overall, maternal immune activation did not alter pig muscle development, but resulted in suppressed innate immune activation. CI - (c) The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Bryan, Erin E AU - Bryan EE AUID- ORCID: 0000-0002-0011-2761 AD - Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA. FAU - Bode, Nick M AU - Bode NM AD - Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA. FAU - Chen, Xuenan AU - Chen X AD - Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA. FAU - Burris, Elli S AU - Burris ES AD - Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA. FAU - Johnson, Danielle C AU - Johnson DC AD - Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA. FAU - Dilger, Ryan N AU - Dilger RN AUID- ORCID: 0000-0003-2538-2845 AD - Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA. FAU - Dilger, Anna C AU - Dilger AC AD - Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL 61802, USA. LA - eng PT - Journal Article PL - United States TA - J Anim Sci JT - Journal of animal science JID - 8003002 RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Lipopolysaccharides) RN - 0 (Interleukin-6) SB - IM MH - Pregnancy MH - Swine MH - Animals MH - Female MH - *Tumor Necrosis Factor-alpha MH - *Lipopolysaccharides/pharmacology MH - Sus scrofa/physiology MH - Weaning MH - Muscle Fibers, Skeletal MH - Interleukin-6 PMC - PMC10794819 OAB - Maternal inflammation or immune activation impacts fetal development and subsequently the offspring's postnatal performance. In particular, maternal immune activation may be detrimental to fetal muscle development and alter postnatal immune responses, both of which are vital in determining livestock efficiency. However, understanding the relationship between maternal immune activation and offspring development is difficult as many models use a live pathogen. This introduces many confounding factors, including increased mortality, persistent postnatal infection, and potential copathogens. Therefore, the objective of this study was to determine the effect of maternal inflammation on offspring muscle development and postnatal inflammatory response using repeated injections of a nonpathogenic immune stimulant. Each injection successfully induced an inflammatory response as indicated by increased rectal temperature and circulating inflammatory markers. The gestational challenge did not result in increased litter mortality. Further, muscle development was not altered in piglets exposed to gestational inflammation. However, when challenged with the same immune stimulant given to the dams, pigs exposed to maternal inflammation had a remarkably suppressed immune response compared to controls. Overall, maternal inflammation independent of infection affected offspring immune function, but not muscle development. OABL- eng OTO - NOTNLM OT - inflammation OT - lipopolysaccharide OT - muscle development OT - prenatal programming COIS- The authors declare no real or perceived conflicts of interest. EDAT- 2024/01/08 12:43 MHDA- 2024/01/19 06:42 PMCR- 2025/01/08 CRDT- 2024/01/08 09:59 PHST- 2023/08/29 00:00 [received] PHST- 2024/01/03 00:00 [accepted] PHST- 2025/01/08 00:00 [pmc-release] PHST- 2024/01/19 06:42 [medline] PHST- 2024/01/08 12:43 [pubmed] PHST- 2024/01/08 09:59 [entrez] AID - 7512741 [pii] AID - skad424 [pii] AID - 10.1093/jas/skad424 [doi] PST - ppublish SO - J Anim Sci. 2024 Jan 3;102:skad424. doi: 10.1093/jas/skad424.