Up-regulated interleukin-4 production by peripheral T-helper cells in idiopathic membranous nephropathy.
BACKGROUND
Helper T (Th) cells are classified into Th1 and Th2 subsets based on cytokine production and the Th1/Th2 paradigm explains differences in inflammatory effector pathways in various human diseases. Membranous nephropathy (MN) is an immune complex disease associated with Th2 nephritogenic immune response. However, overproduction of interleukin (IL)-4, a principal Th2 cytokine, has not been demonstrated. We investigated Th1/Th2 cytokine production by peripheral Th cells and its association with the degree of proteinuria in MN.


METHODS
We analysed production of Th1/Th2 cytokines, interferon (IFN)-gamma and IL-4 by peripheral Th cells, using an intracellular cytokine detection method with flow cytometry in patients with MN (n = 24). The data were compared with data from healthy subjects (n = 51), subjects with minimal change nephrotic syndrome (MCNS; n = 13) and subjects with focal segmental glomerulosclerosis (FSGS; n = 12). We compared the percentages of IFN-gamma+ and IL-4+ Th cells and the peripheral Th1/Th2 ratio (IFN-gamma/IL-4 ratio) among the four groups. We also examined the association of IFN-gamma and IL-4 production with clinical parameters of MN.


RESULTS
The mean percentage of IL-4+ cells in MN (3.9+/-1.2%) was significantly higher than in the control (2.4+/-1.0%), MCNS (2.3+/-1.4%) and FSGS (2.3+/-1.2%) groups (P<0.001, respectively). The Th1/Th2 ratio was significantly lower in MN (5.3+/-2.0) than in the control (8.2+/-4.2, P<0.05), MCNS (10.0+/-5.3, P<0.01) and FSGS (10.2+/-5.3, P<0.01) groups. Moreover, the percentage of IL-4+ cells correlated significantly with the amount of proteinuria in MN (r = 0.57, P<0.01).


CONCLUSIONS
IL-4 production by peripheral Th cells is up-regulated in patients with MN and correlated with the severity of proteinuria. Intracellular cytokine analysis could be a useful index in idiopathic MN.
Masutani
Kohsuke
K
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. masutani@kcu.med.kyushu-u.ac.jp
Taniguchi
Masatomo
M
Nakashima
Hitoshi
H
Yotsueda
Hideki
H
Kudoh
Yuji
Y
Tsuruya
Kazuhiko
K
Tokumoto
Masanori
M
Fukuda
Kyoichi
K
Kanai
Hidetoshi
H
Hirakata
Hideki
H
Iida
Mitsuo
M
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000378:metabolism*; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009401:Nephrosis / Q000378:metabolism*; D011507:Proteinuria / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*; D015854:Up-Regulation
D007074:Immunoglobulin G; D015847:Interleukin-4; D007371:Interferon-gamma