Osteoarthritis: auto-inflammation, IL-17 and the microbiome

Osteoarthritis pain occurs when there is a chronic inflammatory response to localized joint tissue stress. As the result of a loss of immune tolerance, there is inflammation and pain out of proportion to the mechanical stress. In most autoimmune diseases  IL-17 (Interleukin-17) is an important proinflammatory agent. In a study published in the Journal of Orthopaedic Translation, authors show that osteoarthritis can be reduced by altering the gut flora in a way that reduces IL-17 production. They had set about that very task:

"To examine the role of interleukin 17 (IL-17) in cartilage destruction during the progression of osteoarthritis (OA), and determine whether regulation of gut commensal flora can attenuate osteoarthritis through IL-17."

Stressed tissue in some elicits a more aggressive inflammatory reaction

The authors analyzed normal and osteoarthritic synovial tissue from human and animal subjects to IL-17 analysis, and manipulated the microbiome of mice subjected to experimental medial meniscus injury to measure OA changes and IL-17 expression with other parameters. They found an important subset that had more aggressive proinflammatory IL-17 activity in response to the tissue stress.

"We found that there is an OA subgroup with enhanced IL-17 expression in synovium. IL-17 increased activities of MMP13 and decreased matrix synthesis in chondrocytes. Intra-articular injection of IL-17 accelerated articular cartilage degradation and high IL-17 expression in MINK1 knock-out mice also accelerated OA development."

Osteoarthritis, inflammation and the gut microbiome

It is of great importance that they also demonstrated that modification of the gut microbiome modulated IL-17 expression and osteoarthritic progression.

"Interestingly, C57BL/6 mice obtained from different microbial conditions displayed difference in IL-17 expression and OA progress. Subsequent 16sRNA sequence analysis demonstrated different composition of gut microbe, including one special bacteria called SFB in the Firmicutes. Regulation of gut microflora by antibiotic attenuated osteoarthritis progress in DMM mice and this alleviation was reversed after colonization of non-SPF mouse fecal microflora."

Clinical bottom line

Osteoarthritis is an autoinflammatory condition characterized by a more aggressive inflammatory response to stressed or damaged tissue, with a subset exhibiting high IL-17 activity, a hallmark of autoimmunity. This may be ameliorated by regulating the autoinflammatory response through manipulation of the gut microbiome. The authors conclude:

"Gut microbe is involved in OA pathology by modulating proinflammatory cytokine IL-17 activity. Regulation of gut microflora maybe a potential therapy in a high IL-17 expression subgroup of OA patients."

For more on osteoarthritis pain see Osteoarthritis is an inflammatory disorder driven by complement and More on the autoimmunity of osteoarthritis.