Neuroprotective effects of noble gases following acquired brain injury: a narrative review.

Osteoarthritis (OA) is the most common degenerative condition worldwide, involving multiple joint tissues, including articular cartilage, synovium, subchondral bone, menisci, ligaments, and the fat pads, all of which contribute to disease initiation and progression and undergo important biomechanical and inflammatory changes through the activation of the innate immune system ().OA has affected nearly 500 million people globally, with the knee joint being the most frequently affected site. The major risk factors for disease initiation are aging, obesity, mechanical injury, genetic changes, and chronic low-grade inflammation (). This immune system activation underscores the importance of understanding the role of inflammatory cytokines, as they are key mediators in cartilage and in the downstream signaling pathways that contribute to disease progression (). The IL-1 family in humans and most mammals includes 11 cytokines, some of which promote inflammation and others reduce it. These IL-1 cytokines are proteins weighing 17–18 kDa, characterized by a β-trefoil pyramidal barrel structure composed of six two-stranded β-hairpins (). The IL-1 family members include IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β, IL-36γ, IL-1Ra, IL-36Ra, IL-37, and IL-38. These cytokines play important roles in the pathogenesis of arthritic disease progression (). These cytokines play an important role in maintaining bone and cartilage homeostasis by modulating the biology of chondrocytes, osteoblasts, and synovial cells. Among them, interleukin-1β (IL-1β) and interleukin-18 (IL-18) are upstream activators due to their strong pro-catabolic effects. Both cytokines initiate autocrine and paracrine inflammatory loops, where IL-1β enhances its own production and acts as a mediator of IL-6 and matrix metalloproteinases (MMPs) (). IL-18 shares structural resemblance with IL-1β, which is why it is classified as part of the IL-1 superfamily. This cytokine primarily originates from an inactive precursor that is converted to functional IL-18 via enzymatic cleavage (). Initially, IL-18, which is upregulated by NK and T cells, was identified as promoting interferon-γ (IFN-γ) production, either alone or in conjunction with IL-12. This led to its designation as an IFN-γ-inducing factor, thereby rapidly activating monocytes and macrophages (). IL-18 directly affects the cartilage as chondrocytes and osteoblasts secrete it. and findings suggest that IL-18 promotes cartilage degradation by increasing the expression of COX-2, iNOS, and MMPs in chondrocytes and stimulates the production of IL-6 and nitric oxide, which promotes matrix degradation (). Consequently, IL-18 creates a harmful environment within the cartilage, characterized by an excess of degradative enzymes and reduced repair capacity ().