Targeting IL‐11 in the treatment of BK virus‐associated haemorrhagic cystitis—A promising new approach

Abstract

The BK polyomavirus (BKPyV) has pathogenic relevance especially in immunocompromised patients. No causal therapy has been established yet. Therefore, new therapeutic targets need to be identified in experimental studies. A 3D organotypic cell culture model with primary urothelial cells and fibroblasts was used as infection model. The detection of virus replication was performed with quantitative polymerase chain reaction (qPCR), and immunohistochemistry (IHC) was also used for analysis. Interleukin levels were measured by enzyme‐linked immunosorbent assay (ELISA). Interestingly, the signal transducer and activator of transcription 3 (STAT3) pathway seems to be activated during infection with BKPyV, for example phosphorylated STAT3 is significantly ( P < 0.0001) elevated on day 6 following infection. Therefore, we performed ELISAs for involved interleukins in STAT3 pathway. Interleukin 11 (IL‐11) was significantly ( P = 0.026) elevated at day 9. Subsequently, 3D cultures were treated with IL‐11 neutralizing antibody. At day 9 following infection, the median virus replication rate is 4.4 × 10 6 copies/ml. The difference to replication rate without treatment was significantly lower at day 6 ( P < 0.0001) and at day 9 ( P < 0.0001), respectively. STAT3 pathways seem to be involved during BKPyV infection and need further investigation in experimental studies. A very promising target for treatment might be IL‐11.

Urinary Tract Infections: Virus

“…The utilization of antibody against IL-11 showed promising in vitro activity against BKV. Although tocilizumab (an anti-IL-6 antibody) did not yield significant results in this study, its role in the treatment of BKV infection will need detailed further exploration, as IL-6 is an important component of the STAT3 pathway ( Schneidewind et al, 2020a , Schneidewind et al, 2020b ). Likewise, it may be expected that further experimental studies focussed on the STAT3 pathway in BKV infection might unveil more potential therapeutic targets.…”

“…Such culture methods will highlight the interactions between BKV and human urothelial cells which might unveil the unknown nuances associated with BKV pathogenesis. Furthermore, they might facilitate the in vitro testing of antiviral drugs against new potential therapeutic targets ( Schneidewind et al, 2020a , Schneidewind et al, 2020b ).…”

Significance of BK Polyomavirus in Long-Term Survivors after Adult Allogeneic Stem Cell Transplantation

“…Recently, approaches for experimental evaluation in long-term survivors of aSCT have been described. Our group reported on interleukin 11 (IL-11), which may represent a promising therapeutic target to treat BKPyV infections [ 24 ]. So far, careful monitoring of kidney function and BKPyV viral load remain the standard of care in the long-term follow up of aSCT patients.…”

Management of BK virus-associated haemorrhagic cystitis in allogeneic stem cell transplant recipients

“…Although tocilizumab (an anti-IL-6 antibody) did not yield significant results in this study, its role in the treatment of BKV infection will need detailed further exploration, as IL-6 is an important component of the STAT3 pathway. 83 Likewise, it may be expected that further experimental studies focussed on the STAT3 pathway in BKV infection might unveil more potential therapeutic targets.…”