IL-18 may play a crucial role in the process of TIF by promoting TEC injury and activation, and could be a target of the therapeutic approaches against TIF.
The aim of this study was to investigate the role of renal Epstein-Barr virus (EBV) infection in the pathogenesis of lupus nephritis (LN). A total of 58 renal tissue samples from patients with LN, seven normal renal tissue samples from patients with non-glomerular hematuria and 37 renal tissue samples from patients with minimal change nephropathy were collected. The expression of EBV-latent membrane protein-1 (EBV-LMP1) and EBV-encoded RNA 1 (EBER-1) in the renal tissue was examined by immunohistochemistry (IHC) and in situ hybridization (ISH), respectively. The sera levels of anti-nuclear antibody as well as antibodies to extractable nuclear antigen in patients with LN were also measured. An equivalence test showed that the results from the IHC and the ISH analyses had strong agreement. The positive rates of renal EBER-1 and EBV-LMP1 in the LN patients were significantly higher than those of the normal and minimal change nephropathy patients (P<0.001), while no significant difference was identified between those of the normal and minimal change nephropathy groups (P>0.05). The positive rates of EBV-LMP1 and EBER-1 in the renal tissues of patients with LN were not determined to be significantly different between the relapse (immunosuppressant-treated) and initial onset (non-treated) patients, between the patients with and without concurrent infection, and among the patients with different age ranges (P>0.05). The proportion of LN patients positive for anti-Sm antibody was significantly higher in the renal EBV-positive group than in the EBV-negative group (P<0.05), while the proportions of LN patients positive for the other autoantibodies that were examined were not identified to be significantly different between these two groups (P>0.05). The present study shows that renal EBV infection may contribute to the pathogenesis of LN by inducing anti-Sm antibody production.
Aim: To study the effect of selective interleukin-1β-converting enzyme (ICE, caspase-1) inhibitor on ischemic acute renal failure (ARF). Methods: Mouse models of ischemic ARF were treated with the specific ICE inhibitor AC-YVAD-CMK. A renal function assay and renal morphological studies were employed to estimate the renal protective effect of AC-YVAD-CMK. The survival rate of mouse models was also analyzed by a time series test. Furthermore, renal ICE activity, mature interleukin-18 (IL-18) protein expression and interferon-γ (IFN-γ) mRNA expression were also detected by fluorescent enzyme-linked immunosorbent assay (ELISA), ELISA, and semi-quantitative reverse transcription-polymerase chain reaction, respectively. Results: The levels of blood urea nitrogen (BUN) and serum creatinine (Scr) increased remarkably in the model controls compared with the sham-operated groups (P<0.01). Typical renal tubular necrosis was found in the model controls. Renal ICE activity, mature IL-18 protein expression, and IFN-γ mRNA expression were also increased significantly in the model controls compared with the sham-operated groups. The levels of BUN and Scr in the AC-YVAD-CMK therapy group were decreased significantly compared with the untreated model controls (P<0.01). Renal tubulointerstitial lesion was also attenuated significantly (P<0.05). AC-YVAD-CMK therapy alleviated the clinical features of ARF, and increased the survival rate (P<0.01). Furthermore, AC-YVAD-CMK therapy also decreased ICE activity, mature IL-18 protein expression, and IFN-γ mRNA expression in renal tissue (P<0.05). Conclusion: The selective ICE inhibitor AC-YVAD-CMK can effectively protect the kidney from acute ischemic lesions. This protective effect is associated with decreased renal ICE activity and suppressed IL-18 maturation and IFN-γ mRNA transcription.
The present study aimed to evaluate the effects of an individualized, low-dose multi-drug immunosuppressive regimen for the treatment of immunoglobulin A nephropathy (IgAN). A preliminary investigation of the course of IgAN following immunosuppressive treatment was conducted based on repeat renal biopsies. Clinical and pathological data of 17 patients with IgAN who received repeat renal biopsies were analyzed retrospectively. In addition to basic treatment, 16 patients regularly received an individualized low-dose immunosuppressive regimen according to their clinical manifestations and pathological patterns following the first biopsy. Clinical parameters, including 24-h urinary protein excretion and levels of serum albumin, uric acid and total cholesterol were collected. Glomerular deposits of IgA and C3, as well as the activity and chronicity indexes of renal lesions were evaluated by semi-quantitative methods. The 24-h urinary protein excretion of the patients decreased significantly from the first biopsy (2.53±2.17 g/day) to the repeated biopsy (0.26±0.55 g/day) (P<0.001). Deposits of IgA and C3 in the glomerulus were persistent, but were reduced in quantity at the second biopsy. Although active renal lesions were observed in the majority of patients, the activity index decreased significantly from 3.18±1.33 prior to therapy to 2.47±0.80 following therapy (P<0.05), while the chronicity index did not change significantly (2.59±2.00 versus 2.76±1.89, respectively). The individualized, low-dose multi-drug immunosuppressive regimen used in the present study significantly minimized proteinuria, stabilized renal function and alleviated histological lesions in patients with IgAN without causing overt adverse effects during the short-term follow-up. In addition to proteinuria, renal pathological changes should be appraised when considering the withdrawal of immunosuppressants from IgAN treatment.
Lupus nephritis (LN) is the most common serious complication of systemic lupus erythematosus (SLE). The pathogenesis of LN is complex, and the majority causes of LN are the renal deposition of circulating or/and in situ-formed immune complexes. These immune complexes trigger glomerular and tubulointerstitial inflammation, which finally leads to proteinuria and loss of renal function. Despite the emergence of new biological agents, cyclophosphamide (CY), an alkylating agent, is still the first-line drug widely used to treat patients with severe LN. In this review, we outline the application history, molecular structure, and pharmacokinetics of CY in the treatment of LN. We also detail its latest known immunopharmacological mechanisms, with a focus on supplemental regulation and inhibition of CD4 and CD8 positive T cells, differences in the use of various guidelines, and the combination with other drugs. The side effects of CY are also mentioned in this review.
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