Ozone Therapy and Immune Markers in Experimental Ulcerative Colitis: A Preclinical Rat Study

This is a preclinical animal study

The work described here was carried out in rats, not people. Findings in animal models of inflammatory bowel disease frequently fail to reproduce in human trials, and nothing on this page should be read as evidence that ozone therapy treats ulcerative colitis or any other bowel condition in humans.

Background: immune dysregulation in inflammatory bowel disease

The researchers frame ulcerative colitis as a disorder of immune regulation, in which the immune system mounts a response against antigens from the person's own intestinal microbiota and against colonic cells altered by inflammation. Two signalling molecules central to that process are interleukin-17 and interleukin-23, both associated with inflammatory activity, and two cell populations of interest are CD4-positive lymphocytes and FoxP3-positive regulatory T cells, which help restrain immune responses.

Given the range of biological effects attributed to ozone, the team set out to test whether ozone administered by two different routes would alter these immune markers at the site of intestinal injury.

Study design: 64 rats, two routes, six days

The study used 64 adult male inbred Wistar rats weighing 240 plus or minus 20 g. Experimental ulcerative colitis was induced using oxazolone, a standard laboratory model that produces mucosal inflammation resembling the human disease.

An ozone-oxygen mixture was administered either intraperitoneally or rectally, at a concentration of 1.0 to 1.2 mg per litre, once daily in a volume of 10 ml, over a six-day course. Measurements were taken on days 2, 4 and 6.

IL-17 and IL-23 concentrations were measured in homogenised intestinal tissue, and CD4 and FoxP3 expression on intestinal lymphocytes was assessed by immunohistochemistry.

Findings

In untreated animals, tissue damage to the large intestine increased steadily from day 2 to day 6. Total lymphocyte numbers rose, while CD4-positive and FoxP3-positive T lymphocytes fell. IL-17 and IL-23 concentrations rose in step with the severity of inflammation.

Intraperitoneal ozone was associated with a significant reduction in lymphocyte content in the damaged tissue by day 6, and CD4-positive and FoxP3-positive T lymphocyte numbers normalised by day 6. The cytokine picture was mixed: IL-17 and IL-23 still rose from day 2 to day 6, with only IL-23 lower on day 6 than in untreated animals.

Rectal ozone brought FoxP3-positive cell numbers back to the levels seen in healthy animals by day 6. Both IL-17 and IL-23 were significantly lower on day 6 than in untreated animals, which the authors attribute to the anti-inflammatory properties of ozone.

Limitations

This was an animal study. The oxazolone model reproduces some features of human ulcerative colitis but not the disease itself, and results in rodent colitis models have a poor record of translating to human patients.

The findings were not uniform across routes. Intraperitoneal ozone reduced IL-23 but not IL-17, and cytokine levels still rose over the six days. This is a more equivocal result than a summary of the conclusions alone would suggest.

The study ran for six days with no longer follow-up, so nothing can be said about durability. The abstract does not describe randomisation or blinding of the assessments. There is no indication of independent replication by another group.

The intraperitoneal route - injection into the abdominal cavity - is a laboratory technique and has no equivalent in home use. The rectal doses used in rats do not translate to human dosing.

Ulcerative colitis is a serious diagnosed condition requiring specialist medical care. Anyone with inflammatory bowel disease should discuss any complementary approach with their gastroenterology team, and should not alter prescribed treatment.

This summary is based on the English-language abstract published by the journal. The full text is in Russian.