A Pilot Study Assessing the Ability of 5-Aminosalicylic Acid to Modulate the Immune Response in Chronic Beryllium Disease.

Chronic beryllium disease is a granulomatous lung disease, characterized by the accumulation of macrophages and beryllium-specific CD4+ T-cells that proliferate and produce T-helper cell type 1 cytokines. Previous studies indicate that beryllium-mediated oxidative stress enhances cytokine response in chronic beryllium disease CD4+ T-cells. 5-Aminosalicylic acid (5-ASA) is currently used to treat inflammatory bowel disease and has both antioxidant and antiinflammatory actions. We hypothesized that 5-ASA therapy may be a beneficial therapy in chronic beryllium disease. An investigator-initiated, randomized, double-blind, placebo-controlled 5-ASA trial was undertaken. Patients with chronic beryllium disease were randomized 3:1 to receive 5-ASA (500-mg capsules) four times daily (n = 13) or placebo capsules (n = 5), for 6 weeks. Primary study endpoints included changes in beryllium lymphocyte proliferation test responses in peripheral blood mononuclear cells and bronchoalveolar lavage cells. Secondary endpoints included changes in bronchoalveolar lavage fluid cells, serum, and peripheral blood mononuclear cell glutathione levels, bronchoalveolar lavage cell-stimulated tumor necrosis factor-α levels, lung function, and quality of life as measured by the Short Form 36 questionnaire. 5-ASA decreased bronchoalveolar lavage cell beryllium lymphocyte proliferation test responses by 20% within the 5-ASA treatment group (P = 0.06), although this was not seen for blood beryllium lymphocyte proliferation test responses. No significant changes were observed in serum, peripheral blood mononuclear cells, bronchoalveolar lavage fluid, or bronchoalveolar lavage cell glutathione levels in either the 5-ASA or placebo treatment group. 5-ASA treatment decreased ex vivo beryllium-stimulated bronchoalveolar lavage cell tumor necrosis factor-α levels within the 5-ASA group (P = 0.06) and when compared with placebo (P = 0.04). Significant improvements were noted in quality of life measurements with 5-ASA treatment. The ability of 5-ASA to decrease bronchoalveolar lavage cell beryllium lymphocyte proliferation test responses and diminish beryllium-stimulated bronchoalveolar lavage cell tumor necrosis factor-α levels suggests that 5-ASA may impact the beryllium-specific immune response in chronic beryllium disease. Clinical trial registered with www.clinicaltrials.gov (NCT01088243).