Role of Interleukin-11 in Various Glomerulonephritis with Heavy Proteinuria

• Main Authors: Jien-Wen Chien, 錢建文
• Other Authors: Ching-Yuang Lin
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/64229788188519221279

碩士 === 國立陽明大學 === 臨床醫學研究所 === 94 === According to polarized specific immune responses mediated by CD4+ T helper (Th) lymphocytes, there are two types of immune response: type 1 (Th1) and type 2 (Th2). There are more and more evidence to support the relevance of Th1 and Th2 responses in human diseases, including various glomerulonephritis. Childhood idiopathic nephrotic syndrome (INS), an example of Th2-mediated renal disease, is thought to be associated with production of Th2-type cytokine with significant effects on vascular permeability. On the other hand, both Th1 and Th2 responses are involved in IgA nephropathy (IgAN) and Lupus nephritis (LN). Interleukin-11 (IL-11) is a pleiotropic cytokine with both hematopoietic and anti-inflammatory effects. The anti-inflammatory effect of IL-11 stems from its ability to reduce macrophage activation and divert the immune response from a Th1 to a Th2 response. Recombinant human IL-11 (rhIL-11) has been tried in a variety of Th1-mediated inflammatory diseases. On the other hand, IL-11 has adverse effects in asthma, which is a Th2-mediated disease. The role of IL-11 in kidney disease had been explored in an animal experiment, where IL-11 was shown to have the ability to reduce macrophage activation and attenuates nephrotoxic nephritis (Th1 disease). Owning to the anti-inflammatory and Th2-driven effects, IL-11 may play a beneficial role in a Th1-mediated disease but a harmful role in a Th2-mediated disease. Thus the purpose of this study is to explore the role of IL-11 in various kidney diseases. Patients with proteinuria (daily urine protein excretion > 40mg/M2/hr) and underlying pathology of IgAN, LN, and INS were included. Daily urine excretion of IL-11 was measured by ELISA method. Correlation between daily urinary IL-11 excretions with daily urinary protein and other clinical parameters were determined by Pearson’s correlation coefficient. Another 5 patients with serial data for daily urinary protein, urinary IL-11 and IL-11 mRNA expression in urine sediment are presented. The correlation between urinary IL-11 and daily urinary protein was significant for patients with IgAN (r = 0.596, p = 0.006) and LN (r = 0.630, p < 0.001), but not for patients with INS (r = 0.030, p = 0.812). Serial data revealed the same correlation for patients with IgAN and LN. Furthermore, urinary IL-11 mRNA expression was elevated before urinary IL-11 increased. Daily urinary IL-11 excretion and IL-11 mRNA expression were correlated with urinary protein loss in nephritis having local Th1 predominant immune response, such as IgAN and LN. Local IL-11 production may serve as a counter cytokine against Th1-mediated inflammation.