Interleukin-6 in chronic renal allograft rejection: influence of nonimmunologic risk factors

Boratyńska, Maria; Klinger, Marian; Szyber, P; Patrzałek, D.; Polak, Katarzyna

doi:10.1016/s0041-1345(00)02393-9

Cited by 7 publications

(8 citation statements)

References 13 publications

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“…IL-6 is a proinflammatory cytokine that has numerous effects on T cell activation, differentiation, and recruitment (66)(67)(68). In the context of transplantation, increased levels of IL-6 correlated with adverse outcomes in human allograft recipients (69,70). IL-6 is known to inhibit the function of natural Tregs (71), as well as the induction of iTregs (52).…”

Section: Discussionmentioning

confidence: 99%

Rapamycin-treated human endothelial cells preferentially activate allogeneic regulatory T cells

Wang¹,

Yi²,

Qin³

et al. 2013

J. Clin. Invest.

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Human graft endothelial cells (ECs) can act as antigen-presenting cells to initiate allograft rejection by host memory T cells. Rapamycin, an mTOR inhibitor used clinically to suppress T cell responses, also acts on DCs, rendering them tolerogenic. Here, we report the effects of rapamycin on EC alloimmunogenicity. Compared with mock-treated cells, rapamycin-pretreated human ECs (rapa-ECs) stimulated less proliferation and cytokine secretion from allogeneic CD4 + memory cells, an effect mimicked by shRNA knockdown of mTOR or raptor in ECs. The effects of rapamycin persisted for several days and were linked to upregulation of the inhibitory molecules PD-L1 and PD-L2 on rapa-ECs. Additionally, rapa-ECs produced lower levels of the inflammatory cytokine IL-6. CD4 + memory cells activated by allogeneic rapa-ECs became hyporesponsive to restimulation in an alloantigen-specific manner and contained higher percentages of suppressive CD4 + CD25 hi CD127 lo FoxP3 + cells that did not produce effector cytokines. In a human-mouse chimeric model of allograft rejection, rapamycin pretreatment of human arterial allografts increased graft EC expression of PD-L1 and PD-L2 and reduced subsequent infiltration of allogeneic effector T cells into the artery intima and intimal expansion. Preoperative conditioning of allograft ECs with rapamycin could potentially reduce immune-mediated rejection.

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Section: Discussionmentioning

confidence: 99%

Rapamycin-treated human endothelial cells preferentially activate allogeneic regulatory T cells

Wang¹,

Yi²,

Qin³

et al. 2013

J. Clin. Invest.

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“…The overproduction of IL-6 leads to the deposit of extracellular matrix proteins, the development of inflammatory lesions, and the synthesis of acute-phase proteins. However, we cannot assume the impact of the overproduction of these proinflammatory cytokines because in the present study their systemic expression was not significant between the groups [31]. With regard to the CRP results, we consider them ambiguous and that the value of the data in relation to the diagnostic precision of the CRP is limited [32].…”

Section: Discussionmentioning

confidence: 96%

The Oxidative and Inflammatory State in Patients with Acute Renal Graft Dysfunction Treated with Tacrolimus

Carrillo-Ibarra

Cerrillos‐Gutiérrez

Escalante-Núñez

et al. 2016

Oxidative Medicine and Cellular Longevity

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Objective. To determine the oxidative stress/inflammation behavior in patients with/without acute graft dysfunction (AGD) with Tacrolimus. Methods. Cross-sectional study, in renal transplant (RT) recipients (1-yr follow-up). Patients with AGD and without AGD were included. Serum IL-6, TNF-α, 8-isoprostanes (8-IP), and Nitric Oxide (NO) were determined by ELISA; C-reactive protein (CRP) was determined by nephelometry; lipid peroxidation products (LPO) and superoxide dismutase (SOD) were determined by colorimetry. Results. The AGD presentation was at 5.09 ± 3.07 versus 8.27 ± 3.78 months (p < 0.001); CRP >3.19 mg/L was found in 21 versus 19 in the N-AGD group (p = 0.83); TNF-α 145.53 ± 18.87 pg/mL versus 125.54 ± 15.92 pg/mL in N-AGD (p = 0.64); IL-6 2110.69 ± 350.97 pg/mL versus 1933.42 ± 235.38 pg/mL in N-AGD (p = 0.13). The LPO were higher in AGD (p = 0.014): 4.10 ± 0.69 µM versus 2.41 ± 0.29 µM; also levels of 8-IP were higher in AGD 27.47 ± 9.28 pg/mL versus 8.64 ± 1.54 pg/mL (p = 0.01). Serum levels of NO in AGD were lower 138.44 ± 19.20 µmol/L versus 190.57 ± 22.04 µmol/L in N-AGD (p = 0.042); antioxidant enzyme SOD activity was significantly diminished in AGD with 9.75 ± 0.52 U/mL versus 11.69 ± 0.55 U/mL in N-AGD (p = 0.012). Discussion. Patients with RT present with a similar state of the proinflammatory cytokines whether or not they have AGD. The patients with AGD showed deregulation of the oxidative state with increased LPO and 8-IP and decreased NO and SOD.

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“…32,33 IL-6, considered as a pro-inflammatory Th2 cytokine, 21 is present in the graft and is elevated in serum or urine with chronic rejection. 14,15 Our working hypothesis was that IL-6 deficiency in the recipients would prevent CVR development. Surprisingly, IL-6 deficiency did not protect against chronic rejection of WT allografts, neither in a WT nor an ApoE-deficient background and rather aggravated CVR in IL-6 Ϫ/Ϫ ApoE Ϫ/Ϫ recipients.…”

Section: Discussionmentioning

confidence: 99%

“…10,11 The IL-6 system is activated within the grafted organ, 12 and an IL-6 increase in the serum is a predictive marker for acute rejection. 13 In chronic rejection, several studies have also shown elevated levels of IL-6 in serum and urine of the patients 14,15 ; however, its role has not been clarified.…”

mentioning

confidence: 99%

Interleukin-6 Deficiency Fails to Prevent Chronic Rejection After Aortic Allografts in Apolipoprotein E–Deficient Mice

Yacoub‐Youssef

Blaes

Calise

et al. 2009

The Journal of Heart and Lung Transplantation

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Interleukin-6 in chronic renal allograft rejection: influence of nonimmunologic risk factors

Cited by 7 publications

References 13 publications

Rapamycin-treated human endothelial cells preferentially activate allogeneic regulatory T cells

Rapamycin-treated human endothelial cells preferentially activate allogeneic regulatory T cells

The Oxidative and Inflammatory State in Patients with Acute Renal Graft Dysfunction Treated with Tacrolimus

Interleukin-6 Deficiency Fails to Prevent Chronic Rejection After Aortic Allografts in Apolipoprotein E–Deficient Mice

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