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-alpha 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.
Institute for Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
Philipp
P
Haas
Rainer H
RH
Straub
Sammy
S
Bedoui
Heike
H
Nave
D000818:Animals; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000097:blood / Q000276:immunology; D002149:Energy Intake; D006098:Granulocytes / Q000187:drug effects* / Q000276:immunology; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D020738:Leptin / Q000008:administration & dosage* / Q000502:physiology; D007958:Leukocyte Count; D008297:Male; D009000:Monocytes / Q000145:classification / Q000187:drug effects* / Q000276:immunology; D009765:Obesity / Q000097:blood* / Q000209:etiology / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000008:administration & dosage; D013851:Thinness / Q000097:blood* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D020738:Leptin; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha