Photo by Rhoda Baer
ROME, ITALY—Interleukin-1β (IL-1β) is a crucial factor in the development of blood-induced cartilage damage, according to research presented at the European League Against Rheumatism Annual Congress (EULAR 2015).
This discovery suggests that therapeutically targeting IL-1β could provide a new way to protect cartilage after a joint bleed, which can occur after joint trauma, major joint surgery, or due to hemophilia.
Whatever the cause, joint bleeds are expected to lead to an inflammatory response in the joint and to significant destruction of joint cartilage. So a treatment that could limit the damage from a joint bleed could potentially minimize future disability.
“As therapeutic agents opposing the activity of IL-1β are readily available, further research is now warranted to investigate whether an IL-1β antagonist would be effective in preventing and treating joint damage as a result of bleeding into the joint,” said study investigator Simon Mastbergen, PhD, of the University Medical Centre Utrecht in the Netherlands.
“Findings also suggest that the quicker treatment is initiated, the less damage to the joint may be sustained.”
Dr Mastbergen and his colleagues presented these findings at EULAR 2015 as abstract OP0262.
The researchers had cultured healthy human cartilage samples for 4 days in the presence or absence of 50% whole blood. They then added an IL-1β monoclonal antibody (mAb), an IL-1 receptor antagonist (IL-1RA), or a TNF-α mAb during blood exposure and assessed subsequent cartilage damage.
The IL-1β mAb and IL-1RA protected cartilage from blood-induced damage in a dose- and time-dependent manner. Early administration after blood exposure was the most beneficial. And, when the treatments were given at higher concentrations, there was near-complete normalization of cartilage.
The researchers said these effects were accompanied by a reduction in IL-1β and IL-6 production. The level of IL-1β was 74 pg/mL in whole-blood culture, but levels were undetectable after the IL-1RA was added (P=0.028). The level of IL-6 was 21,347 pg/mL in whole-blood culture, 27 pg/mL after the IL-1RA was added, and 289 pg/mL after the IL-1β mAb was added (P=0.028 for both).
However, TNF-α levels were unaffected by the IL-1RA or IL-1β mAb. TNF-α levels wer 35 pg/mL in whole-blood culture and 37 pg/mL after the addition of the IL-1RA or IL-1β mAb (P=0.753 for both).
Of course, the TNF-α mAb inhibited the effects of TNF-α on cartilage, but the mAb had no significant effect on blood-induced cartilage damage.
“This would appear to rule out TNF-α inhibitors, a class of drug currently used to treat various forms of arthritis, for this new indication,” Dr Mastbergen said.
