Protective effects of pre-treatment with exogenous porcine glucagon-like peptide-2 and its microspheres of piglets with lipopolysaccharide-induced intestinal inflammation

Abstract

Context Glucagon-like peptide-2 (GLP-2) is an intestinotrophic growth hormone that can accelerate intestinal development and recovery from injury. However, the half-life of GLP-2 is short, thus it must be administered frequently. Moreover, its effects during weaning are unclear. Aims We tested the effects of porcine GLP-2 (pGLP-2) and pGLP-2 microspheres on lipopolysaccharide (LPS)-induced intestinal inflammation in weaning piglets. Methods Eighteen female weaning piglets aged 21 days (5.38 ± 0.72 kg initial bodyweight) were randomly assigned to three treatment groups: (1) control, (2) GLP-2, and (3) GLP-2 microsphere (MS) group. Control piglets were injected intraperitoneally with 3 mL of saline solution from Days 1 to 7, GLP-2 piglets were injected intraperitoneally with 100 μg pGLP-2/kg bodyweight from Days 1 to 7, and MS piglets were injected intraperitoneally with 200 mg GLP-2 microspheres on Day 1 and with 3 mL saline solution from Days 2 to 7. On Day 8, all piglets were injected with 100 μg LPS/kg bodyweight. Key results Piglets in the GLP-2 and MS groups showed markedly increased average daily weight gain on Day 7, decreased serum myeloperoxidase, LPS and keratinocyte growth factor levels, and increased serum interleukin-10 levels compared with the control group. In addition, the GLP-2 group showed decreased myeloperoxidase content in the duodenum and ileum, and reduced caspase-3 activity in the duodenum and jejunum, whereas MS piglets showed decreased myeloperoxidase levels and suppressed caspase-3 activity in the duodenum and jejunum. Moreover, administration of pGLP-2 or pGLP-2 microspheres resulted in decreased interleukin-8 and interferon-γ mRNA expression levels in the jejunum, as compared with the control group. Conclusions Our results indicated that pGLP-2 promotes growth, and ameliorates LPS-induced serum and intestinal inflammatory responses in piglets. Furthermore, pGLP-2 microspheres can achieve similar therapeutic effects as pGLP-2 under the premise of fewer injections. Implications pGLP-2 microspheres have considerable potential for the treatment of weaning-induced intestinal inflammation in piglets.