The Beneficial Effects of Oral Cotrimoxazole upon Likely Biomarkers of Oxidative Stress in Advanced Fibrotic Lung Disease

Abstract

Introduction: In cases of idiopathic pulmonary fibrosis, we have observed an elevation in mean red cell volume, serum gamma glutamyl transferase and peripheral monocyte counts, initially in a pilot study but also in new incident cases. These changes could not be explained by drug therapy, vitamin deficiency or other diseases. Method: We compared the peripheral blood abnormalities in 149 patients with lung fibrosis to 448 age and sex matched controls. We also examined the effect of cotrimoxazole treatment for 12 weeks on these abnormalities. From the pilot study of cotrimoxazole in lung fibrosis patients, the relationship of the peripheral blood monocyte count and serum cytokine transforming growth factor beta-1 was examined. Epstein Barr viral status was examined in a selection of patients in case it explained our observations. Results: The findings confirm the elevation in mean red cell volume, gamma glutamyl transferase and peripheral monocyte counts in patients compared with matched controls. Oral cotrimoxazole ameliorated these 3 blood abnormalities. Serological evidence of Epstein Barr viral infection was present in tested patients but active viral replication was absent. The monocyte count had a linear relationship with the serum transforming growth factor beta-1 levels, which increased by 600 pg/ml for every of 0.1 × 10 9 /l increase in the monocyte count. Conclusion: These observations may reflect oxidative stress which was reduced by cotrimoxazole. A related sulphonamide "dapsone" is known to reduce oxidative stress through direct effects on neutrophil and mo-nocyte function; similar effects may explain these findings and require a formal study.