5-Aminosalicylic Acid Modulates the Immune Response in Chronic Beryllium Disease Subjects
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Chronic beryllium disease (CBD) is characterized by accumulation of macrophages and beryllium-specific CD4+ T cells that proliferate and produce Th1 cytokines. 5-Amino salicylic acid (5-ASA) is currently used to treat inflammatory bowel disease and has both antioxidant and anti-inflammatory actions. We hypothesized that 5-ASA may be a beneficial therapeutic in CBD.
Seventeen CBD patients were randomized 3:1 to receive 5-ASA 500-mg capsules or placebo four times daily for 6 weeks orally. Primary study endpoints included changes in beryllium lymphocyte proliferation (BeLPT). Secondary endpoints included changes in bronchoalveolar lavage (BAL) fluid, cells, serum, and blood cell glutathione (GSH) levels, BAL cell TNF-α levels, lung function, and quality of life measures.
5-ASA decreased BAL cell BeLPT by 20% within the 5-ASA treatment group. No significant changes were observed in serum, PBMCs, BALF, or BAL cell GSH levels in either the 5-ASA or placebo treatment group. 5-ASA treatment decreased ex vivo Be-stimulated BAL cell TNF-α levels within the 5-ASA group and when compared to placebo. Significant improvements were noted in quality of life measurements with 5-ASA treatment.
5-ASA’s ability to decrease BAL cell BeLPT and Be-stimulated BAL cell TNF-α levels suggests that 5-ASA may impact the beryllium-specific immune response in CBD. 5-ASA use in other non-infectious granulomatous lung diseases, such as sarcoidosis, may prove to be a useful alternative treatment to corticosteroids for those with mild to moderate disease.
KeywordsBerylliosis 5-Aminosalicylic acid Granuloma Lung TNF-alpha Therapeutic trial (or therapy) Quality of life
NIH RO1 012504, RO1 ES017582, R01 ES023826, and P01 ES11810. This publication was supported by NIH/NCATS Colorado CTSA Grant Number UL1TR001082 from the National Center for Research Resources. Its contents are the authors’ sole responsibility and do not necessarily represent official NIH views.
Study design: Drs. LAM, BJD. Data collection: BB, JH, CTRC. Data analysis and interpretation: BB, JE, MG, and LL. Manuscript development: Drs. LAM, BJD, and BQB. We extend our thanks to the participants in this study, Charles Ferris, PhD, E. Brigitte Gottschall, MD for their assistance with the study.
Compliance with Ethical Standards
Conflict of interest
Dr. Brian Day declares that he has received research grants from the NIH and is an inventor on an issued US Patent for use of 5-ASA in the treatment of granulomatous lung disease. Dr. Lisa Maier has received research grants from the NIH. Dr. Jie Huang, Mrs. Briana Barkes, Mrs. May Gillespie, and Dr. Li Li declare no conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the National Jewish Health institutional review board (IRB) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.