| Abstract No.: | A-B1049 |
| Country: | Canada |
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| Title: | LEPTIN ENHANCES LIPOPOLYSACCHARIDE-INDUCED CYTOKINE RELEASE IN RAT MICROGLIAL PRIMARY CULTURES. |
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| Authors/Affiliations: | 1 Veronique Lafrance*; 1 Wataru Inoue; 2 Steve Poole; 1 Giamal Luheshi;
1 Douglas University Mental Health Institute, Montreal, QC, Canada; 2 NIBSC, Potters Bar, United Kingdom
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| Content: | Leptin, an adipocyte-derived hormone, regulates food intake and energy expenditure via actions in the brain. In addition to its central effect on energy homeostasis, leptin has been implicated in immune function and inflammation. Previously we have shown that administration of leptin causes fever, a typical brain-regulated inflammatory response, through the induction of the pro-inflammatory cytokine interleukin (IL)-1beta in the brain. More recently, we demonstrated that in vivo, lipopolysaccharide (LPS)-induced fever as well as LPS-induced brain IL-1beta were partially mediated by leptin, implicating this hormone in LPS-induced inflammation. However, leptin’s inflammatory mechanisms and targets in the brain remain unclear. In the periphery leptin alone or in combination with LPS enhances cytokine production in monocytes and macrophages. We hypothesized therefore that it has a similar action in the brain by targeting microglia, the resident macrophages in the central nervous system (CNS), especially since we demonstrated recently that leptin induced IL-1beta in microglia in vitro. Objectives: The aim of our study was to investigate the role of leptin in the inflammatory response of microglia treated with LPS and whether it acts as a modulator in the brain as it does in the periphery. Materials and Methods: Primary cultures of microglia were incubated with leptin (1microg/ml) for 24 hours prior to adding LPS (0.1microg/ml) or saline for 3 hours. The release of cytokines in the medium was measured by ELISA. Heat-treated leptin was used as a negative control. Results: As expected, leptin induced IL-1beta release into the medium and had an additive effect on the LPS-induced IL-1beta release. This result was further supported by studying TNF-alpha release from the same cells, which interestingly was not induced by leptin alone but was significantly enhanced when leptin was added in combination with LPS, when compared to LPS alone. These effects were completely abolished when leptin was neutralized by heat-treatment. Conclusion: These results demonstrate that leptin in combination with LPS stimulated IL-1beta and TNF-alpha release from microglia in a more efficient way than LPS alone. This suggests that leptin modulates the inflammatory response of microglia to LPS in a similar way as it does on peripheral macrophages. |
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