Source:Journal of Allergy and Clinical Immunology
Author(s): Gunther Spohn, Natalia Arenas-Ramirez, Gregory Bouchaud, Onur Boyman
BackgroundParticular neutralizing monoclonal antibodies to certain cytokines act as agonists in vivo by protection of the cytokine's active site and prolongation of cytokine half-life. While this principle might be useful for targeted immunotherapy, its role in the pathogenesis of inflammation and autoimmunity is unclear.ObjectiveWe sought to determine whether slight, structurally non-relevant modifications of the prototypic pro-inflammatory cytokine interleukin-1β (IL-1β) during an immune response could elicit polyclonal anti-IL-1β antibody responses that modulated IL-1β's in vivo activity.MethodsWe engineered two different IL-1β variants, thereby mimicking the process of cytokine modification occurring during inflammation, and conjugated them to virus-like particles, followed by immunization of mice. The resulting polyclonal anti-IL-1β antibody responses were assessed using in vitro and in vivo assays as well as two relevant (auto-) inflammatory murine models.ResultsWhile antibody responses generated to one variant were potently inhibiting IL-1β, antibody responses induced by the other variant even potentiated the in vivo effects of IL-1β; the latter led to enhanced morbidity in two different IL-1β-mediated mouse models, including a model of inflammatory bowel disease and an inflammatory arthritis model.ConclusionThese data demonstrate that endogenous polyclonal anti-cytokine antibody responses can enhance the cytokine's activity in inflammatory and autoimmune diseases.
Teaser
Capsule summary: Polyclonal anti-cytokine autoantibodies, endogenously generated during an anti-virus-like immune response, can boost, rather than neutralize, pro-inflammatory cytokines thus exacerbating (auto-) inflammatory disorders.http://ift.tt/2eO23DB
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