Background/Purpose: Inflammation within sacroiliac joints and within the spine is a hallmark of ankylosing spondylitis (AS). Apart from nonsteroidal anti-rheumatic drug (NSAID) treatment, inhibition of TNF, but not of IL-6, has been proven successful in the treatment of signs and symptoms of AS. In addition to its direct inflammatory role, some cytokines might particularly affect bone metabolism. For instance, IL-23 can induce bone formation involving IL-22 as a secondary mediator.

 To determine the potential involvement of several inflammatory mediators such as cytokines like IL-23, IL-22, IL-12, IL-6, IL-10 and prostaglandins in the inflammation-driven joint remodeling process in AS, we determined their expression within the cartilage, the subchondral bone and within entheses in zygapophyseal joints of patients with ankylosing spondylitis. Furthermore, we determined their expression within the subchondral bone marrow and within fibrous tissue, which we find in joints undergoing joint remodeling.

Methods: Expression of IL-6, IL-10, IL-12, IL-22, IL-23 as well as of PGE2 and its receptor EP2 were determined by immunohistochemistry in zygapophyseal joints of patients with ankylosing spondylitis (n=13 patients with AS), and in 9 patients with osteoarthritis (OA) and in zygapophysel joints of 10 autopsy controls (CO). AS patients joints were obtained from patients undergoing polysegmental correction surgery because of hyperkyphosis. 

Results:

The number of IL-6-expressing cells within the cartilage and bone marrow were reduced in AS joints compared to controls (p<0.005). The number of IL-10+ cells was reduced within cartilage and the entheses in AS joints (p<0.005 and p<0.01), but increased in osteocytes found within the subchondral bone plate (p<0.01). Numbers of IL-12+ cells were not significantly different between AS and the control groups. IL-22 was reduced within the cartilage and entheses in AS joints compared to autopsy controls (p<0.001 and p<0.01). Numbers of IL-23+ cells were reduced at enthesial sites of AS joints (p<0.05) compared to autopsy controls but not within cartilage or subchondral bone. Prostaglandin E2 expression and expression of the receptor EP2 was high within cartilage in general and particularly high within the fibrous tissue (i.e. about 90% of cells were positive within subchondral fibrous tissue of AS joints), which is not present in healthy joints obtained from autopsy controls .

Conclusion:

In contrast to IL-23 and IL-17 (Appel et al. ARD, 2011, 2013), which are highly expressed within the subchondral bone marrow of AS joints we found no increase in IL-6 expression.

Within cartilage and/or entheses we rather find a reduction in IL-10, IL-22 and IL-23 expression which might reflect the disturbed homeostasis of the cartilage in the AS joints undergoing joint remodeling, i.e. intraarticular ankylosis. The high prostaglandin E2 expression and EP2 expression within the fibrous tissue might indicate that prostaglandins are involved in the putative pathological role of this tissue promoting joints remodeling. NSAIDs, which seem to retard radiographic spinal progression might block the pathogenic activity of this subchondral fibrous tissue.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/analysis-of-inflammatory-markers-within-facet-joints-of-patients-within-ankylosing-spondylitis/