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

Abstract

The objective was to determine 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 until GD 84 with initial dose of 10 μg LPS/kg BW increasing by 12% each time to prevent endotoxin tolerance. On GD 70, 76, and 84, blood was collected at 0 and 4 h post-injection 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 pig closest to litter body weight average was used for dissection and muscle fiber characterization. On weaning (postnatal day 21), pigs were weighed individually and two barrows closest to litter body weight average were selected another study. The third barrow closest to litter body weight average was selected for the postnatal LPS challenge. On postnatal day 52, pigs were given 5 μg LPS/kg BW via intraperitoneal injection, and blood was collected at 0, 4, and 8 h post-injection to determine TNF-α concentration. INFLAM gilt TNF-α concentration increased (P < 0.01) 4 h post-injection compared to 0 h post-injection, while CON gilt TNF-α concentration did not differ between time points. INFLAM gilt IL-6 and IL-1β concentrations increased (P = 0.03) 4 h post-injection compared to 0 h post-injection 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) 4 h post-injection. TNF-α concentration did not differ between treatments at 0 and 8 h post-injection, but CON pigs had increased (P = 0.01) TNF-α compared to INFLAM pigs 4 h post-injection. Overall, maternal immune activation did not alter pig muscle development, but resulted in suppressed innate immune activation.