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Leptin regulates leukocyte recruitment into the brain following systemic LPS-induced inflammation

Molecular Psychiatry volume 15, pages 523–534 (2010)Cite this article

Abstract

The appetite suppressing hormone leptin has emerged as an important modulator of immune function and is now considered to be a critical link between energy balance and host defense responses to pathogens. These ‘adaptive’ responses can, in situations of severe and sustained systemic inflammation, lead to adverse effects including brain damage that is partly mediated by neutrophil recruitment into the brain. We examined the contribution of leptin to this process in leptin-deficient (ob/ob), -resistant (db/db) and wild-type (WT) mice injected intraperitoneally with a septic dose of lipopolysaccharide (LPS). This treatment induced a dramatic increase in the number of neutrophils entering the brain of WT mice, an effect that was almost totally abolished in the mutant mice and correlated with a significant reduction in the mRNA levels of interleukin-1β, intracellular adhesion molecule-1 and neutrophil-specific chemokines. These effects were reversed with leptin replenishment in ob/ob mice leading to recovery of neutrophil recruitment into the brain. Moreover, 48 h food deprivation in WT mice, which decreased circulating leptin levels, attenuated the LPS-induced neutrophil recruitment as did a single injection of an anti-leptin antiserum 4 h before LPS treatment in WT mice. These results provide the first demonstration that leptin has a critical role in leukocyte recruitment to the brain following severe systemic inflammation with possible implications for individuals with altered leptin levels such as during obesity or starvation.

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Acknowledgements

We thank Ms G Somay for excellent technical assistance. This study was supported by the Canadian Institute of Health Research and the Natural Sciences and Engineering Research Council of Canada (GNL). CR is a fellow of the Deutsche Forschungsgemeinschaft (DFG project RU 1397/1-1). WI is a recipient of a PhD scholarship from the Nakajima Foundation, Japan.

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  1. C Rummel

    Present address: 3Current address: Department of Veterinary-Physiology, Justus-Liebig-University Giessen, Frankfurter Strasse 100, Giessen D-35392, Germany.,

  2. C Rummel and W Inoue: These authors contributed equally to the work.

Authors and Affiliations

  1. Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada

    C Rummel, W Inoue & G N Luheshi

  2. Department of Endocrinology, National Institute for Biological Standards and Control, Potters Bar, UK

    S Poole

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Correspondence to G N Luheshi.

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Rummel, C., Inoue, W., Poole, S. et al. Leptin regulates leukocyte recruitment into the brain following systemic LPS-induced inflammation. Mol Psychiatry 15, 523–534 (2010). https://doi.org/10.1038/mp.2009.98

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