Effect of Azithromycin on the level of interleukin-23, interleukin-17 in serum of rats with Adriamycin-induced nephrosis

Abstract

Objective To explore the effect of Azithromycin on the immune mechanisms through the IL-23/IL-17 axis way by observing the changes in serum levels of IL-23, IL-17 in rats with Adriamycin-induced nephrosis. Methods A total of 135 rats were randomly divided into control group, model group, Azithromycin intervention group, Prednisone intervention group and united intervention group.The model was induced through a tail intravenous injection of Adriamycin for 2 times.Nine rats were randomly selected from every group to detect blood and urinary biochemistry, and to observe the changes of the serum levels of IL-23, IL-17 by enzyme-linked immunosorbent assay in 4, 6, and 8 weeks. Results Compared with the model group in the 8th week, the levels of 24-hour urinary protein[model group(354.83±70.87) mg/d, Azithromycin intervention group(94.59±22.67) mg/d, Prenisone intervention group(65.64±8.71) mg/d, united intervention group(47.44±9.56) mg/d], cholesterol [model group(8.71±1.60) mmol/L, Azithromycin intervention group(3.54±0.30) mmol/L, Prenisone intervention group(3.10±0.18) mmol/L, united intervention group(2.56±0.40) mmol/L]were reduced significantly, while the levels of albumin[model group(16.77±3.15) g/L, Azithromycin intervention group(33.82±1.16) g/L, Prenisone intervention group(37.80±2.73) g/L, united intervention group(40.78±2.63) g/L] were increased obviously in the intervention groups, and the differences were statistically significant(F=152.243, 99.838, 155.836, all P<0.05). The serum levels of IL-23[model group(29.60±3.97) ng/L, Azithromycin intervention group(29.61±2.62) ng/L, Prenisone intervention group(29.74±2.23) ng/L, united intervention group(30.31±2.20) ng/L], IL-17[model group(22.38±2.51) ng/L, Azithromycin intervention group(21.97±1.89) ng/L, Prenisone intervention group(21.43±2.42) ng/L, united intervention group(21.51±2.07) ng/L]in the model group and 3 intervention groups were higher than the control group[(17.35±3.01) ng/L, (14.03±2.42) ng/L] in the 4th week, and there were significant differences (F=33.819, 21.373, all P<0.05); and the levels of IL-23[in the 6th week, Azithromycin intervention group(27.20±1.71) ng/L, Prenisone intervention group(24.39±2.06) ng/L, united intervention group(21.41±1.71) ng/L, model group(35.78±3.21) ng/L; in the 8th week, Azithromycin intervention group(24.60±2.91) ng/L, Prenisone intervention group(21.01±1.02) ng/L, united intervention group(18.93±1.35) ng/L, model group(44.47±7.84) ng/L], IL-17[in the 6th week, Azithromycin intervention group(19.12±0.37) ng/L, Prenidone intervention group(18.54±0.36) ng/L, united intervention group(17.57±0.42) ng/L, model group(26.69±3.70) ng/L; in the 8th week, Azithromycin intervention group(17.44±0.46) ng/L, Prenidone intervention group(16.37±0.49) ng/L, united intervention group(14.71±0.99) ng/L, model group(34.03±3.45) ng/L]in the 3 intervention groups were significantly lower than those of the model group in the 6th, 8th week(F=82.963, 44.659 in the 6th week, F=75.085, 200.383 in the 8th week, all P<0.05). The levels of IL-23, IL-17 in united intervention group were lower than those in respective intervention groups (P<0.05), and the levels in Prednisone intervention group were lower than those in Azithromycin intervention group(P<0.05). Conclusions IL-23/IL-17 axis' high activity may be one of the immunologic mechanisms of Adriamycin-induced nephrosis.Azithromycin may inhibit the high activity of IL-23/IL-17 axis to relieve the Adriamycin-induced nephrosis.The inhibition on IL-23/IL-17 axis of Azithromycin was similar to Prednisone, and Azithromycin may enhance the effectiveness of Prednisone. Key words: Adriamycin-induced nephrosis; Nephrotic syndrome; Azithromycin; Interleukin-23; Interleukin-17