Relationship between plasma leptin or soluble cleaved leptin-receptor concentrations and glucocorticoid sensitivity of peripheral blood mononuclear cells in patients with nephrotic syndrome.
Leptin is a small peptide hormone which centrally regulates weight. Leptin receptor (OB-R) is expressed in hematopoietic cells, the central nervous, and immune systems. OB-R bears a homology similar to members of the class Iota cytokine family, and therefore, leptin appears to modulate immune responses. The aim of this study was to examine the effect of plasma leptin, soluble OB-R (sOB-R), and the free leptin index (FLI), the ratio between leptin and sOB-R levels, on the sensitivities of peripheral blood mononuclear cells (PBMCs) to prednisolone and cyclosporine in 16 healthy subjects and seven nephrotic syndrome (NS) patients. The NS patients had significantly higher serum sOB-R and lower FLI, compared with the healthy subjects (respectively, P=0.0026, P=0.0383). Whereas, the NS patients had significantly lower PBMC sensitivity to prednisolone (P=0.0049). PBMCs sensitivity to cyclosporine was not significantly different between the healthy subjects and the NS patients. In addition, when the data from all subjects were analyzed, there was a significantly positive correlation between plasma sOB-R concentrations and the IC50 values of prednisolone (P=0.0478). In contrast, plasma leptin concentrations and FLIs did not correlate significantly with the prednisolone and cyclosporine IC50 values. From these observations it can be suggested that plasma leptin has little effect on PBMC sensitivity to immunosuppressive drugs in NS patients. Molecular background(s) for the influence of sOB-R on the PBMC sensitivity to glucocorticoids remain(s) to be elucidated.
Henmi
Kayo
K
Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. y984164@educs.ps.toyaku.ac.jp
Yoshida
Masaharu
M
Yoshikawa
Noriko
N
Nakabayashi
Iwao
I
Hirano
Toshihiko
T
D000328:Adult; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020738:Leptin / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000097:blood*; D011239:Prednisolone / Q000494:pharmacology*; D054411:Receptors, Leptin / Q000097:blood*
D007166:Immunosuppressive Agents; D020738:Leptin; D054411:Receptors, Leptin; D011239:Prednisolone