Proinflammatory Polarization of Macrophages Causes Intestinal Inflammation in Low-Birth-Weight Piglets and Mice

Background: Low-birth-weight (LBW) animals suffer from intestinal damage and inflammation in their early life.Objectives: The aim of this study was to investigate the role of macrophages in intestinal inflammation in LBW piglets and mice.Methods: Major genes involved in intestinal barrier function such as claudin-1, zonula occludens-1 (ZO-1), occludin, and mucin 2 and in-flammatory cytokines such as IL-1 & beta;, TNF-& alpha; , IL-10, and IL-13 were evaluated in 21-day-old, normal-birth-weight (NBW) and LBW piglets and mice. Macrophage markers such as CD16/32, CD163, and CD206 were also assessed by immunofluorescence and flow cytometry. Polarized and unpolarized macrophages were further transferred into NBW and LBW mice, followed by an evaluation of intestinal permeability and inflammation.Results: Claudin-1 mRNA in LBW piglets as well as claudin-1, occludin, ZO-1, and mucin 2 mRNAs in LBW mice, was significantly down-regulated. IL-1 & beta; and TNF-& alpha; were significantly upregulated in LBW piglets (P < 0.05). LBW mice showed a reduced expression of IL-10 and IL-13 (P < 0.05), with a heightened IL-6 level (P < 0.01) in the jejunum. CD16, a marker for M1 macrophages, was significantly elevated in the jejunum of LBW piglets, whereas CD163, a marker for M2 macrophages, was significantly decreased (P < 0.05). Similarly, LBW mice had more CD11b thorn CD16/32 thorn M1 macrophages (P < 0.05) and fewer CD206 thorn M2 macrophages (P < 0.01) than NBW mice. Moreover, the transfer of M1 macrophages exacerbated intestinal inflammation in LBW mice. Furthermore, 2 major glycolysis-associated genes, hexoki-nase 2 (HK2) and lactate dehydrogenase A (LDHA), were significantly upregulated in LBW piglets and mice (P < 0.05). Conclusions: This study revealed for the first time that the intestinal macrophages are polarized toward a proinflammatory phenotype in LBW piglets and mice, contributing to intestinal inflammation. The findings of this study provide new options for the management of in-testinal inflammation in LBW animals.