Peripheral but not central leptin treatment increases numbers of circulating NK cells, granulocytes and specific monocyte subpopulations in non-endotoxaemic lean and obese LEW-rats

Leptin, a hormone mainly generated by adipocytes, acts centrally in the hypothalamus to regulate body weight and energy expenditure. However, there is strong evidence that leptin is also involved in cell-mediated immunity and cytokine crosstalk. In the present study the effects of diet-induced obesity and central and peripheral leptin treatment on leukocyte subsets and cytokine production was investigated. Leptin was injected either intravenously (i.v.) or intracerebroventricularly (i.c.v.) in male endotoxaemic or vehicle-treated healthy LEW-rats. Numbers of blood leukocyte subsets were analysed by FACS and cytokines (TNF-alpha and IL-6) by ELISA. Results showed that peripheral rather than central leptin treatment was able to significantly increase numbers of granulocytes. NK cells and monocytes. Three-colour staining revealed that the increase of ED9(+) monocytes was most likely due to the mobilization of two distinct monocyte subsets. predominantly ED9(+)CD4(-)NKR-P1A(+) and ED9(+)CD4(+)NKR-P1A(+). ELISA analysis revealed significantly elevated TNF-a levels in obese animals compared to their lean littermates, while IL-6 failed to show notable changes. In conclusion. the data of the present study revealed that leptin application induces a nutrition- and application-site dependent increase of circulating NK cells. granulocytes and specific monocyte subsets. (C) 2008 Elsevier B.V. All rights reserved.