Impact of interleukin-6 on T cells in kidney transplant recipients

Abstract

Interleukin-6 (IL-6), a multifunctional proinflammatory cytokine, plays a key role in T cell activation, survival, and differentiation. Acting as a switch that induces the differentiation of naïve T cells into Th17 cells and inhibits their development into regulatory T cells, IL-6 promotes rejection and abrogates tolerance. Therapies that target IL-6 signaling include antibodies to IL-6 and the IL-6 receptor and inhibitors of janus kinases; several of these therapeutics have demonstrated robust clinical efficacy in autoimmune and inflammatory diseases. Clinical trials of IL-6 inhibition in kidney transplantation have focused primarily on its effects on B cells, plasma cells, and HLA antibodies. In this review, we summarize the impact of IL-6 on T cells in experimental models of transplant and describe the effects of IL-6 inhibition on the T cell compartment in kidney transplant recipients.

IL-6 inhibition prevents costimulation blockade-resistant allograft rejection in T cell-depleted recipients by promoting intragraft immune regulation in mice

“…IL-6 has a prominent role in driving the alloresponse and is a key cytokine regulating the Treg: Teff balance 32 , 33 . Moreover, anti-IL6(R) mAbs are already in clinical use.…”

“…Blocking IL-23 (and interleukin-12) has demonstrated partial therapeutic efficacy when combined with CTLA4-Ig in a skin graft model 64 . As IL-6 has a prominent role in driving the alloresponse 32 , 65 and is a key cytokine regulating the Treg: Teff balance 33 we focused on IL-6 as a therapeutic target. We show that neutralizing IL-6 mitigates ongoing inflammatory responses within cardiac allografts and allows Tregs to accumulate.…”

Non‐directed (altruistic) kidney donation: Altruism or insurance policy?

“…The same study found that overall cumulative incidence of ESRD at 20 years postdonation, 25 years postdonation and 30 years postdonation was 0.5%, 1.1% and 1.5%, respectively. 18 Various other studies, each involving thousands (one involving over 120,000) of living kidney donors, found comparable results. [19][20][21] These studies suggest that while, compared to healthy non-donors, living kidney donors have an increased risk of ESRD, the magnitude of the increase in absolute risk is small.…”

“…With regard to end‐stage renal disease (ESRD) following living kidney donation, a study of 158,304 such donors in the United States found that 589 (0.37%) experienced ESRD (37.2 per 10,000 donors). The same study found that overall cumulative incidence of ESRD at 20 years postdonation, 25 years postdonation and 30 years postdonation was 0.5%, 1.1% and 1.5%, respectively 18 . Various other studies, each involving thousands (one involving over 120,000) of living kidney donors, found comparable results 19–21 .…”