Gene polymorphism in IL-1 receptor antagonist affects its production by monocytes in IgA nephropathy and Henoch-Schonlein nephritis.
OBJECTIVE
To define the functional significance of IL-1 receptor antagonist (IL-1ra) gene polymorphism and to investigate, the production of IL-1ra by monocytes from individuals with different genotypes of IL-1.


METHODS
The genotype of IL-1ra was detected by polymerase chain reaction (PCR). Peripheral monocytes obtained from patients with immunoglobin A nephropathy (IgAN), Henoch-Schonlein purpura nephritis (HSPN) and normal subjects were matched in sex and age between the IL1RN-2 allele carriers and non-carriers. The secretion of IL-1ra, IL-1 alpha and IL-1 beta in the supernatant of GM-CSF (10 ng/ml) treated and untreated monocytes were measured by ELISA.


RESULTS
The secretion of IL-1ra by monocytes stimulated with GM-CSF was significantly higher in the IL1RN-2 allele non-carriers than those of carriers both in IgAN (21.55 +/- 3.08 vs 13.85 +/- 2.24 ng/ml, P < 0.001) and HSPN (23.72 +/- 6.68 vs 12.67 +/- 2.24 ng/ml, P < 0.01) as well as in normal controls (20.29 +/- 1.45 vs 10.51 +/- 2.3 ng/ml, P < 0.001). All showed no significant differences in monocyte secretion of IL-1 alpha and IL-1 beta by GM-CSF stimulation between the IL1RN-2 allele carriers and non-carriers.


CONCLUSIONS
These results indicate that a functional correlation of the IL1RN-2 allele and IL-1ra production is present in patients with IgAN and HSPN. This gene polymorphism control of IL-1ra production may contribute to the variety of clinical responses to inflammatory stimulation in individuals with different genotype of IL-1ra.
Liu
Z
Z
Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China. Zhihong@public1.ptt.js.cn
Yang
J
J
Chen
Z
Z
Gong
R
R
Li
L
L
D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D011695:IgA Vasculitis / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D009393:Nephritis / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012795:Sialoglycoproteins / Q000235:genetics* / Q000378:metabolism
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D004247:DNA