A FUSION PROTEIN OF INTERLEUKIN-4 AND INTERLEUKIN-10 PROTECTS AGAINST BLOOD-INDUCED CARTILAGE DAMAGE IN VITRO AND IN VIVO
(Abstract release date: 05/19/16)
EHA Library. van Vulpen L. 06/11/16; 135225; S469
Lize F. D. van Vulpen
Contributions
Contributions
Abstract
Abstract: S469
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 12:00 - 12:15
Location: Room H4
Background
Joint damage upon bleeding causes significant morbidity in patients with hemophilia, and adds to joint degeneration after trauma and major joint surgery. Interleukin (IL)-4 and IL-10 have been demonstrated to protect cartilage from blood-induced damage independently. Recently a novel fusion protein of both cytokines, IL4-10 synerkine, has been developed.
Aims
To evaluate whether IL4-10 synerkine protects against blood-induced joint damage similarly as the combination of the individual components, both in vitro as well as in vivo.
Methods
In vitro, human cartilage explants were exposed to 50% v/v whole blood for 4 days and simultaneously to a broad concentration range (0-100ng/mL) of the IL4-10 synerkine. Effects of 10 ng/mL IL4-10 synerkine were compared to the same concentrations of the individual cytokines and the combination. Cartilage matrix proteoglycan turnover (proteoglycan synthesis, release, and content) was assessed after a recovery period of 12 days. Moreover, the influence of IL4-10 synerkine and its individual components on levels of IL-1β and IL-6 were investigated in a 4 days 50% v/v whole blood culture.In hemophilia A mice, a joint bleed was introduced on day 0 and 14. Mice were randomized between intra-articular treatment with synerkine (7pmol), IL-4&IL-10 (both 7pmol) or PBS on day 0, 2,14 and 16. After 5 weeks, joint damage was evaluated by the Valentino score for synovitis (hematoxylin and eosin-stained sections) and the modified OARSI score for cartilage damage (Safranin O-stained sections).
Results
In vitro, the synerkine prevented blood-induced cartilage damage in a dose-dependent manner up to normalization already at a concentration of 1 ng/mL (see figure). At 10ng/mL, the synerkine was equally effective as the combination of the separate cytokines. IL-1β and IL-6 release in whole blood cultures was suppressed. In vivo, treatment with the synerkine attenuated cartilage damage upon joint bleeding (difference between experimental and contralateral joint in synerkine group p=0.201; IL-4&IL-10 p=0.008; PBS p=0.001). In all groups, synovial inflammation was statistically significantly increased in the experimental paw, none of the treatments affected this (p<0.005 in all groups).
Conclusion
The IL4-10 synerkine fully prevented blood-induced cartilage damage in a human cartilage tissue in vitro model and ameliorated cartilage degeneration upon a repeated joint bleed in haemophilic mice when injected intra-articularly. These data support the need for further investigation of the potency of the IL4-10 synerkine in the treatment of blood-induced arthropathy.
Session topic: Bleeding disorders
Keyword(s): Complications, Cytokine, Hemophilia
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 12:00 - 12:15
Location: Room H4
Background
Joint damage upon bleeding causes significant morbidity in patients with hemophilia, and adds to joint degeneration after trauma and major joint surgery. Interleukin (IL)-4 and IL-10 have been demonstrated to protect cartilage from blood-induced damage independently. Recently a novel fusion protein of both cytokines, IL4-10 synerkine, has been developed.
Aims
To evaluate whether IL4-10 synerkine protects against blood-induced joint damage similarly as the combination of the individual components, both in vitro as well as in vivo.
Methods
In vitro, human cartilage explants were exposed to 50% v/v whole blood for 4 days and simultaneously to a broad concentration range (0-100ng/mL) of the IL4-10 synerkine. Effects of 10 ng/mL IL4-10 synerkine were compared to the same concentrations of the individual cytokines and the combination. Cartilage matrix proteoglycan turnover (proteoglycan synthesis, release, and content) was assessed after a recovery period of 12 days. Moreover, the influence of IL4-10 synerkine and its individual components on levels of IL-1β and IL-6 were investigated in a 4 days 50% v/v whole blood culture.In hemophilia A mice, a joint bleed was introduced on day 0 and 14. Mice were randomized between intra-articular treatment with synerkine (7pmol), IL-4&IL-10 (both 7pmol) or PBS on day 0, 2,14 and 16. After 5 weeks, joint damage was evaluated by the Valentino score for synovitis (hematoxylin and eosin-stained sections) and the modified OARSI score for cartilage damage (Safranin O-stained sections).
Results
In vitro, the synerkine prevented blood-induced cartilage damage in a dose-dependent manner up to normalization already at a concentration of 1 ng/mL (see figure). At 10ng/mL, the synerkine was equally effective as the combination of the separate cytokines. IL-1β and IL-6 release in whole blood cultures was suppressed. In vivo, treatment with the synerkine attenuated cartilage damage upon joint bleeding (difference between experimental and contralateral joint in synerkine group p=0.201; IL-4&IL-10 p=0.008; PBS p=0.001). In all groups, synovial inflammation was statistically significantly increased in the experimental paw, none of the treatments affected this (p<0.005 in all groups).
Conclusion
The IL4-10 synerkine fully prevented blood-induced cartilage damage in a human cartilage tissue in vitro model and ameliorated cartilage degeneration upon a repeated joint bleed in haemophilic mice when injected intra-articularly. These data support the need for further investigation of the potency of the IL4-10 synerkine in the treatment of blood-induced arthropathy.
Session topic: Bleeding disorders
Keyword(s): Complications, Cytokine, Hemophilia
Abstract: S469
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 12:00 - 12:15
Location: Room H4
Background
Joint damage upon bleeding causes significant morbidity in patients with hemophilia, and adds to joint degeneration after trauma and major joint surgery. Interleukin (IL)-4 and IL-10 have been demonstrated to protect cartilage from blood-induced damage independently. Recently a novel fusion protein of both cytokines, IL4-10 synerkine, has been developed.
Aims
To evaluate whether IL4-10 synerkine protects against blood-induced joint damage similarly as the combination of the individual components, both in vitro as well as in vivo.
Methods
In vitro, human cartilage explants were exposed to 50% v/v whole blood for 4 days and simultaneously to a broad concentration range (0-100ng/mL) of the IL4-10 synerkine. Effects of 10 ng/mL IL4-10 synerkine were compared to the same concentrations of the individual cytokines and the combination. Cartilage matrix proteoglycan turnover (proteoglycan synthesis, release, and content) was assessed after a recovery period of 12 days. Moreover, the influence of IL4-10 synerkine and its individual components on levels of IL-1β and IL-6 were investigated in a 4 days 50% v/v whole blood culture.In hemophilia A mice, a joint bleed was introduced on day 0 and 14. Mice were randomized between intra-articular treatment with synerkine (7pmol), IL-4&IL-10 (both 7pmol) or PBS on day 0, 2,14 and 16. After 5 weeks, joint damage was evaluated by the Valentino score for synovitis (hematoxylin and eosin-stained sections) and the modified OARSI score for cartilage damage (Safranin O-stained sections).
Results
In vitro, the synerkine prevented blood-induced cartilage damage in a dose-dependent manner up to normalization already at a concentration of 1 ng/mL (see figure). At 10ng/mL, the synerkine was equally effective as the combination of the separate cytokines. IL-1β and IL-6 release in whole blood cultures was suppressed. In vivo, treatment with the synerkine attenuated cartilage damage upon joint bleeding (difference between experimental and contralateral joint in synerkine group p=0.201; IL-4&IL-10 p=0.008; PBS p=0.001). In all groups, synovial inflammation was statistically significantly increased in the experimental paw, none of the treatments affected this (p<0.005 in all groups).
Conclusion
The IL4-10 synerkine fully prevented blood-induced cartilage damage in a human cartilage tissue in vitro model and ameliorated cartilage degeneration upon a repeated joint bleed in haemophilic mice when injected intra-articularly. These data support the need for further investigation of the potency of the IL4-10 synerkine in the treatment of blood-induced arthropathy.
Session topic: Bleeding disorders
Keyword(s): Complications, Cytokine, Hemophilia
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 12:00 - 12:15
Location: Room H4
Background
Joint damage upon bleeding causes significant morbidity in patients with hemophilia, and adds to joint degeneration after trauma and major joint surgery. Interleukin (IL)-4 and IL-10 have been demonstrated to protect cartilage from blood-induced damage independently. Recently a novel fusion protein of both cytokines, IL4-10 synerkine, has been developed.
Aims
To evaluate whether IL4-10 synerkine protects against blood-induced joint damage similarly as the combination of the individual components, both in vitro as well as in vivo.
Methods
In vitro, human cartilage explants were exposed to 50% v/v whole blood for 4 days and simultaneously to a broad concentration range (0-100ng/mL) of the IL4-10 synerkine. Effects of 10 ng/mL IL4-10 synerkine were compared to the same concentrations of the individual cytokines and the combination. Cartilage matrix proteoglycan turnover (proteoglycan synthesis, release, and content) was assessed after a recovery period of 12 days. Moreover, the influence of IL4-10 synerkine and its individual components on levels of IL-1β and IL-6 were investigated in a 4 days 50% v/v whole blood culture.In hemophilia A mice, a joint bleed was introduced on day 0 and 14. Mice were randomized between intra-articular treatment with synerkine (7pmol), IL-4&IL-10 (both 7pmol) or PBS on day 0, 2,14 and 16. After 5 weeks, joint damage was evaluated by the Valentino score for synovitis (hematoxylin and eosin-stained sections) and the modified OARSI score for cartilage damage (Safranin O-stained sections).
Results
In vitro, the synerkine prevented blood-induced cartilage damage in a dose-dependent manner up to normalization already at a concentration of 1 ng/mL (see figure). At 10ng/mL, the synerkine was equally effective as the combination of the separate cytokines. IL-1β and IL-6 release in whole blood cultures was suppressed. In vivo, treatment with the synerkine attenuated cartilage damage upon joint bleeding (difference between experimental and contralateral joint in synerkine group p=0.201; IL-4&IL-10 p=0.008; PBS p=0.001). In all groups, synovial inflammation was statistically significantly increased in the experimental paw, none of the treatments affected this (p<0.005 in all groups).
Conclusion
The IL4-10 synerkine fully prevented blood-induced cartilage damage in a human cartilage tissue in vitro model and ameliorated cartilage degeneration upon a repeated joint bleed in haemophilic mice when injected intra-articularly. These data support the need for further investigation of the potency of the IL4-10 synerkine in the treatment of blood-induced arthropathy.
Session topic: Bleeding disorders
Keyword(s): Complications, Cytokine, Hemophilia
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