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Clinical Trial Am J Transplant
. 2022 Dec;22 Suppl 4:28-37. doi: 10.1111/ajt.17207.
Importance of IL-6 inhibition in prevention and treatment of antibody-mediated rejection in kidney allografts
Stanley C Jordan 1, Noriko Ammerman 1, Edmund Huang 1, Ashley Vo 1
Affiliations expand
PMID: 36453709 DOI: 10.1111/ajt.17207
Abstract
Interleukin-6 (IL-6) is a cytokine critical for innate and adaptive immune responses. However, persistent expression of high levels of IL-6 are associated with a number of pathologic conditions including autoimmune diseases and capillary leak syndrome. Importantly, in kidney transplant patients, IL-6 may play a role in mediation of cell-mediated rejection (CMR) and antibody-mediated rejection (AMR). This is likely due to the importance of IL-6 in stimulating B cell responses with pathogenic donor-specific antibody (DSA) generation and stimulation of T effector cell responses while inhibiting T regulatory cells. Data from preliminary clinical trials and clinical observations show that tocilizumab (anti-IL-6R) and clazakizumab (anti-IL-6) may have promise in treatment of CMR, AMR and chronic (cAMR). This has led to a phase 3 placebo, randomized clinical trial of clazakizumab for treatment of cAMR, a condition for which there is currently no treatment. The identification of IL-6 production in vascular endothelia cells after alloimmune activation reveals another potential pathway for vasculitis as endothelia cell IL-6 may stimulate immune cell responses that are potentially inhibitable with anti-IL-6/IL-6R treatment. Importantly, anti-IL-6/IL-6R treatments have shown the ability to induce Treg and Breg cells in vivo which may have potential importance for prevention and treatment of DSA development and allograft rejection.

Keywords: clinical research/practice; cytokines/cytokine receptors; immunosuppression/immune modulation; immunosuppressive regimens - maintenance.