Hyaluronic Acid, an Anti-Inflammatory Agent?

Hyaluronic acid is one of the active components of the extracellular matrix and belongs to the family of glycosaminoglycans. Predominantly produced by mesenchymal cells, or stem cells, it can also be synthesized by activated fibroblasts in the dermis. By occupying the spaces between cells, hyaluronic acid contributes to tissue hydration and cohesion. It also plays a role in controlling inflammation. Depending on its molecular weight, location, and certain cellular factors, the binding of hyaluronic acid to proteins can have opposing effects: pro- or anti-inflammatory.

Hyaluronic acid can notably interact with specific cytokines and thus modulate the function of immune cells. Interleukin-8 (IL-8), released by fibroblasts, macrophages, and endothelial and epithelial cells in the presence of inflammation, is an example. Studies in vitro conducted with human keratinocytes have shown that cells treated with hyaluronic acid produced less interleukin-8. The use of this active ingredient could therefore be advantageous in inhibiting an undesirable immune response.

Furthermore, hyaluronic acid has a strong affinity for the CD44 receptor, allowing it to prevent the release of pro-inflammatory cytokines and the synthesis of matrix metalloproteinases (MMP) and prostaglandin E2 (PGE2). These inflammatory molecules, which cause skin redness and itching, are also involved in the onset of musculoskeletal disorders such as osteoarthritis. Hyaluronic acid can also interact with the RHAMM receptor, playing a significant role in inflammation and tissue repair. Located on the surface of cells, RHAMM interacts with CD44 and modulates cell motility, healing, and signal transduction. At the intracellular level, RHAMM binds to actin filaments and the mitotic spindle, thus affecting crucial cellular processes in tumorigenesis, encompassing all stages leading to tumor formation.

Finally, the smallest fragments of hyaluronic acid can bind to Toll-like receptors TLR2 and TLR4, also orchestrating the inflammatory response. Indeed, these molecules are involved in the recruitment and activation of protein complexes leading to the activation of the nuclear factor kappa B (NF-κB) and the induction of inflammatory cytokines. As a reminder, NF-κB is a key transcription factor regulating a set of genes involved in inflammation such as the tumor necrosis factor-α (TNF-α), interleukins 1, 6 and 12, and cyclooxygenase-2 (COX-2).

Due to its involvement in numerous inflammation processes, hyaluronic acid has been the subject of various studies evaluating its effectiveness in treating certain inflammatory skin conditions such as the rosacea and the psoriasis. The results of these studies are presented in the following table.

Hyaluronic acid can also be used to alleviate joint pain, particularly those caused by osteoarthritis. The primary cause of mobility loss, this disease affects 65% of individuals over the age of 65 and is characterized by the destruction of cartilage and inflammation of the membrane lining the inside of the joint. To restore the lubrication and the viscoelastic properties of the synovial fluid, some hospitals offer viscosupplementation, which involves injecting hyaluronic acid directly into the joints. Generally yielding good results (pain reduction, improved mobility, decreased need for pain and inflammation medication...), these injections can only provide temporary relief (between 3 and 12 months) and are less effective than corticosteroid injections.