Abstract
Background and Aims: Hypothermia is observed after administration of high doses of lipopolysaccharide (LPS), yet the mechanisms underlying this response remain incompletely understood. We investigated whether loss of signal regulatory protein α (SIRPα), an inhibitory receptor expressed in macrophages and microglia, affects thermometabolic responses to systemic LPS challenge.
Methods: SIRPα knockout (KO) and wild-type (WT) mice received an intraperitoneal injection of LPS (2 mg/kg). Body temperature, locomotor activity, oxygen consumption (VO2), carbon dioxide production (VCO2), energy expenditure (EE), and respiratory exchange ratio (RER) were assessed. Gene expression of pro- and anti-inflammatory cytokines was quantified in the hypothalamus, meninges, and liver 6 h after injection.
Results: After LPS injection, body temperature, VO2, EE, and locomotor activity were significantly decreased in SIRPα KO mice compared with WT controls. Six hours after LPS injection, expression levels of Tnf, Il1b, and Il10 were significantly higher in the hypothalamus and meninges of SIRPα KO mice than in WT mice, whereas hepatic Tnf expression was significantly lower in SIRPα KO mice than in WT mice.
Conclusions: Enhanced cytokine responses in the hypothalamus and meninges of SIRPα KO mice are associated with exaggerated hypothermic and hypometabolic responses to systemic LPS challenge, potentially through actions on hypothalamic thermoregulatory circuits and/or vagal afferent pathways.
