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.