The effect of chronic, non-pathogenic maternal immune activation on offspring postnatal muscle and immune outcomes.

Abstract

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 10μg 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 4h postinjection via jugular or ear venipuncture to determine tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β 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 5μg LPS/kg BW via intraperitoneal injection, and blood was collected at 0, 4, and 8h postinjection to determine TNF-α concentration. INFLAM gilt TNF-α concentration increased (P<0.01) 4h postinjection compared to 0h postinjection, while CON gilt TNF-α concentration did not differ between time points. INFLAM gilt IL-6 and IL-1β concentrations increased (P=0.03) 4h postinjection compared to 0h 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-α concentration did not differ across time, while CON pig TNF-α concentration peaked (P=0.01) 4h postinjection. TNF-α concentration did not differ between treatments at 0 and 8h postinjection, but CON pigs had increased (P=0.01) TNF-α compared to INFLAM pigs 4h postinjection. Overall, maternal immune activation did not alter pig muscle development, but resulted in suppressed innate immune activation.