TY - JOUR T1 - Differences in Reactivation of Tuberculosis Induced from Anti-TNF Treatments Are Based on Bioavailability in Granulomatous Tissue A1 - Marino, Simeone A1 - Sud, Dhruv A1 - Plessner, Hillarie A1 - Lin, Philana Ling A1 - Chan, John A1 - Flynn, JoAnne L A1 - Kirschner, Denise E Y1 - 2007/10/19 N2 - Author SummaryTuberculosis (TB) is the leading cause of death due to infectious disease in the world today. It is estimated that 2 billion people are currently infected, and although most people have latent infection, reactivation occurs due to factors such as HIV-1 and aging. Antibiotic treatments exist; however, there is still no cure and the current vaccine has proven to be unreliable. Experimental science has uncovered a plethora of immune factors that help the host control infection and maintain latency. One such factor, tumor necrosis factor alpha (TNF), is a protein that facilitates cell–cell communication during an inflammatory immune response. Animal models have shown that TNF is necessary for control of TB infection. Different types of anti-TNF drugs were developed for patients with non-TB related inflammatory diseases such as rheumatoid arthritis and Crohn's disease. Some of these patients who had latent TB suffered reactivation, especially with one drug type. Because these studies cannot be performed in the mouse, and nonhuman primates are expensive, we developed a computational model to perform virtual clinical trials (VCTs) that predicted why reactivation occurs and why it happens differentially between the two classes of drugs tested. We make recommendations on how this issue can be combated. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 3 IS - 10 UR - https://doi.org/10.1371/journal.pcbi.0030194 SP - e194 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.0030194 ER -