The era foregrounded macrophage-driven signaling as the core driver of chronic inflammation, highlighting cross-talk between macrophages and synovial cells that fuels tissue remodeling through collagenase and prostaglandin release. Macrophage-derived mediators such as macrophage colony-stimulating factor and interleukin-1 feed synovial targets, linking immune signaling to arthritic damage and sustained inflammation. Prostaglandins and eicosanoids emerged as central mediators, with prostaglandin pathways showing both pro- and anti-inflammatory potential when modulated; researchers investigated agents affecting prostaglandin synthesis and receptor signaling, including prostaglandin E1-related pathways. Acute-phase signaling programs coordinate systemic inflammatory responses via interleukin-1– and tumor necrosis factor–like mediators, driving hepatic C-reactive protein production across cell types and models. Chronic inflammatory arthritis models demonstrated how local antigen-driven immunity sustains inflammation and autoimmunity, revealing mechanisms of persistent synovitis and collagen autoimmunity. Complement and prostaglandin-like mediators were found to interact, suggesting integrated control of inflammatory signaling through crosstalk between the complement system and prostaglandin pathways.