Anti-inflammatory Effect of Ozone Therapy in an Experimental Model of Rheumatoid Arthritis

To verify the influence of ozone (O₃) therapy on an experimental model of rheumatoid arthritis (RA), 30 male Wistar rats were randomly allocated to 2 groups, control (C) and treatment (T), and subdivided into control (C12, C48, C72) and treatment (T12, T48, T72) groups. RA was induced by administration of collagenase plus complete Freud's adjuvant in the knee joint region. The animals were treated with ozone therapy (1 ml O₃ injection in the knee i.a.) according to group assignment: T12, 2 h; T48, 2 and 24 h; and T72, 2, 24, and 48 h post-RA induction. The different animal groups were euthanized 12, 24, or 72 h post-RA induction, respectively. Synovial exudate levels of IL-10, IL-12p70, TNF-α, INF-γ, and MCP-1 were assessed by flow cytometry, and histopathological analysis of the knee cartilage was conducted. Ozone therapy effectively decreases inflammation, reducing IL-12 and TNF-α, and increasing IL10. O₃ did not statistically affect INF-γ or MCP-1 levels. More expressive results were obtained with group T72, i.e., treated 2, 24, and 48 h post-RA induction, which indicates that longer-term ozone treatment is more effective than a single acute application. Ozone therapy effectively reduced inflammation with effects, at least in part, mediated through reduction of pro-inflammatory cytokines and activation of IL-10 anti-inflammatory cytokine.