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Regulation of insulin and interleukin-1 release after Propionibacterium acnes-induced macrophage activation in mice
A P Bautista1, D J Fletcher, A Volkman
1Department of Pathology, East Carolina University School of Medicine, Greenville, North Carolina.
Abstract:
The administration of a potent activator of macrophages (M phi), Propionibacterium acnes, in nondiabetic mice was associated with the release of significant amounts of interleukin-1 (IL-1) in the peritoneal cavity and plasma within 4 hours after treatment. Shortly before IL-1 peaks were observed, the levels of pancreatic insulin, [3H]leucine-proinsulin, and insulin/total protein ratio were elevated, and followed by a transient but marked hyperinsulinemia at 4 hours after treatment. A single dose of recombinant murine IL-1 in mice was also associated with a 2- to 9-fold increase in the levels of insulin in the pancreas and plasma at 4 hours after treatment. During the period of observation after the administration of P. acnes, plasma glucose levels in treated mice were significantly less than in parallel controls. Mild hypoglycemia was observed at 7 to 10 days posttreatment. Although circulating IL-1-like activity could not be detected in plasma 1 to 10 days after P. acnes treatment, this activity was measured in activated peritoneal and liver M phi. IL-1-like activity (specific activity: 276 units/mg protein) was detected in plasma, after it was chromatographed on a Sephadex G-150 column to remove proteins with higher molecular weight. Peritoneal and liver M phi from P. acnes mice were also able to elaborate significant amounts of IL-1-like activity in their supernatants with or without Escherichia coli lipopolysaccharide. At the same time, total protein synthesis and insulin content in the pancreas in P. acnes mice were significantly lower than the parallel control (p less than 0.01). These results suggest that P. acnes-induced M phi activation in mice was associated with the modulation of insulin release and glucose homeostasis which may be attributed to the accumulation and release of IL-1 by activated M phi.
Insights
Propionibacterium acnes activates macrophages, leading to interleukin-1 release and altered insulin and glucose levels in mice. This suggests a link between macrophage activation and metabolic regulation.
Area of Science:
- Immunology
- Endocrinology
- Metabolic Research
Background:
- Propionibacterium acnes (P. acnes) is known to activate macrophages.
- Interleukin-1 (IL-1) is a key inflammatory cytokine with diverse biological effects.
Purpose of the Study:
- To investigate the effects of P. acnes-induced macrophage activation on insulin release and glucose homeostasis in mice.
- To explore the role of IL-1 in mediating these metabolic changes.
Main Methods:
- Administration of P. acnes to nondiabetic mice.
- Measurement of IL-1 levels in peritoneal fluid and plasma.
- Assessment of pancreatic insulin, proinsulin, and plasma glucose levels.
- Analysis of IL-1-like activity in macrophages and plasma.
- Evaluation of pancreatic protein synthesis.
Main Results:
- P. acnes treatment led to significant IL-1 release and transient hyperinsulinemia.
- Recombinant IL-1 administration also increased insulin levels.
- Plasma glucose levels were reduced in P. acnes-treated mice, with mild hypoglycemia observed later.
- IL-1-like activity was detected in activated macrophages and, after purification, in plasma.
- Pancreatic insulin content and protein synthesis were reduced in P. acnes-treated mice.
Conclusions:
- P. acnes-induced macrophage activation modulates insulin release and glucose homeostasis.
- Interleukin-1 accumulation and release by activated macrophages likely contribute to these metabolic alterations.
- This study highlights a potential link between immune activation and metabolic dysregulation.