PIONEERING research has demonstrated that the use of dual cytokine blockers can mitigate toxic reactions, including graft-versus-host-disease (GVHD) and other inflammatory disorders. The novel study led by researchers from UC Davis Health, Sacramento, California, USA, has shown that blocking IL-6 and TNF cytokines provides an effective approach to treating life-threatening GVHD.
The treatment of some blood disorders and cancers requires allogeneic haematopoietic stem cell transplantation (allo-HSCT). This entails the infusion of a donor’s bone marrow stem cells into a patient who is undergoing chemotherapy and radiation therapy. These immune cells are intended to illicit an attack against the patients’ tumour; however, in GVHD the transplanted cells attack the patients’ healthy tissues, resulting in potentially lethal effects.
TNF and IL-6 represent two inflammatory cytokines that play a key role in both autoimmunity and excessive immune reactions to viruses. Current approaches to GVHD treatment focus on the targeted blocking on one of these cytokines to prevent an inflammatory cytokine storm.
The novel research led by senior study author, William Murphy, University of California, Davis, USA, is the first to evaluate the potential of a combined approach blocking both cytokines. “Surprisingly, only a single cytokine blockade to IL-6 or TNF was evaluated in preventing GVHD, which gave disappointing clinical results. Given the important and possibly redundant roles these powerful inflammatory cytokines play, it makes sense that combination approaches would be needed for greater efficacy,” Murphy explained.
Murphy and his team tested combined TNF and IL-6 treatment in post-allo-HSCT and obese mouse models with severe cytokine release syndrome. They found that the combined blocking resulted in improved protection against GVHD severity and related mortality. Furthermore, analysis found that the blockade of both citations did not impair the intended impacts of the allo-HSCT, the graft-versus-tumour effects.
The study has wider implications in improving the efficacy of treatment for pro-inflammatory disease, something especially relevant amid the ongoing COVID-19 pandemic. “The increased efficacy of combined blockade suggests that this approach to treating diseases caused by inflammation may have greater benefit in other clinical settings,” summarised Murphy.