We have located links that may give you full text access.
Endogenous polyclonal anti-IL-1 antibody responses potentiate IL-1 activity during pathogenic inflammation.
BACKGROUND: Particular neutralizing mAbs to certain cytokines act as agonists in vivo through protection of the cytokine's active site and prolongation of its half-life. Although this principle might be useful for targeted immunotherapy, its role in the pathogenesis of inflammation and autoimmunity is unclear.
OBJECTIVE: We sought to determine whether slight, structurally nonrelevant modifications of the prototypic proinflammatory cytokine IL-1β during an immune response could elicit polyclonal anti-IL-1β antibody responses that modulated IL-1β's in vivo activity.
METHODS: We engineered 2 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 by using in vitro and in vivo assays, as well as 2 relevant (auto-) inflammatory murine models.
RESULTS: Although 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 2 different IL-1β-mediated mouse models, including a model of inflammatory bowel disease and an inflammatory arthritis model.
CONCLUSION: These data demonstrate that endogenous polyclonal anti-cytokine antibody responses can enhance the cytokine's activity in inflammatory and autoimmune diseases.
OBJECTIVE: We sought to determine whether slight, structurally nonrelevant modifications of the prototypic proinflammatory cytokine IL-1β during an immune response could elicit polyclonal anti-IL-1β antibody responses that modulated IL-1β's in vivo activity.
METHODS: We engineered 2 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 by using in vitro and in vivo assays, as well as 2 relevant (auto-) inflammatory murine models.
RESULTS: Although 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 2 different IL-1β-mediated mouse models, including a model of inflammatory bowel disease and an inflammatory arthritis model.
CONCLUSION: These data demonstrate that endogenous polyclonal anti-cytokine antibody responses can enhance the cytokine's activity in inflammatory and autoimmune diseases.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app