Oxygen-Ozone Therapy and Pro-Inflammatory Cytokine Levels in Musculoskeletal and Temporomandibular Disorders: A Review

Background

Musculoskeletal conditions such as low back pain, knee osteoarthritis and rheumatic disease, along with temporomandibular disorders (TMD) affecting the jaw joint and surrounding muscles, are among the most common causes of persistent pain and disability. A shared feature of these conditions is chronic inflammation, in which the body releases signalling proteins called pro-inflammatory cytokines. One of these, interleukin-6 (IL-6), is closely linked to ongoing pain and tissue damage. Oxygen-ozone (O2-O3) therapy, in which a controlled mixture of oxygen and ozone gas is delivered locally, has been proposed as a way to dampen this inflammatory activity, and this review set out to examine what the published evidence shows.

Study design

This is a comprehensive narrative review rather than a systematic review or a new clinical trial. The authors gathered and summarised existing studies that measured serum pro-inflammatory cytokine levels, principally IL-6, in patients treated with oxygen-ozone therapy. The literature they drew on spanned several conditions, including temporomandibular disorders, low back pain and disc herniation, knee osteoarthritis, and rheumatic diseases such as rheumatoid arthritis. Across the studies reviewed, ozone was typically administered as an oxygen-ozone gas mixture given by local injection, for example into or around an affected joint or along the spine, with the aim of reducing inflammation at the site of pain. The authors also discussed the proposed biochemical mechanisms behind these effects.

Findings

The evidence gathered in the review suggested that oxygen-ozone therapy was associated with lower serum levels of pro-inflammatory cytokines, and interleukin-6 in particular, across the conditions examined. The authors describe a proposed mechanism in which controlled, moderate exposure to ozone triggers the body's own antioxidant defences and, in turn, tempers the inflammatory signalling that drives pain. However, the studies behind these observations were relatively few, varied in their design and methods, and generally small, so the authors treated the pattern as promising rather than established.

What the authors concluded

The authors concluded that oxygen-ozone therapy may help reduce pro-inflammatory cytokine levels, especially IL-6, in musculoskeletal and temporomandibular disorders, and that it could represent a useful complementary option for managing inflammation-related pain. They were careful to add that the current evidence is limited and that further, higher-quality studies are needed to clarify the size and reliability of these effects.

Limitations of this study

As a narrative review, this paper did not follow the structured, exhaustive search and appraisal methods of a systematic review, so relevant studies may have been missed and the selection was not formally standardised. The underlying evidence was heterogeneous: study designs, ozone protocols, dosing and follow-up periods differed, sample sizes were often small, and the findings were not pooled in a meta-analysis. Because of this, the review reports an encouraging but preliminary signal rather than firm proof, and its conclusions should be read as a summary of early evidence rather than a definitive verdict on effectiveness.