Tenofovir attenuates cytokine storm and bronchiolar damage in a mouse model of bleomycin-induced acute lung injury.

SARS-CoV-2 pandemic has converged with the HIV epidemic. Although immunocompromised patients show an elevated risk of death due to COVID-19 compared to HIV infection, the impact remains contradictory. One reason could be the use of antiretroviral therapy (ARV). Patients with HIV receiving ARV, such as tenofovir (TDF), have fewer symptoms of COVID-19. In mice, bleomycin (BLM) induces acute lung injury, resulting in an acute inflammatory response similar to the cytokine storm and lung damage observed in COVID-19. This study aimed to evaluate the preventive role of TDF administration prior to BLM administration. A total of 64 eight-week-old C57BL/6J mice (Charles River, France), both male and female, were randomly assigned to four experimental groups (n = 8 per sex per group): (i) oral TDF administered in drinking water from day 0 to day 7, followed by oropharyngeal aspiration (OA) of saline on day 7 (TDF); (ii) oral TDF in drinking water from day 0 to day 7, followed by OA of bleomycin on day 7 (TDF-BLM); (iii) regular drinking water throughout the experiment, followed by OA of saline on day 7 (SAL); and (iv) regular drinking water throughout the experiment, followed by OA of bleomycin on day 7 (BLM). Animals were euthanized 72 h after OA (day 10), and serum and lung tissues were collected for analysis. TDF-BLM lungs showed significantly reduced bronchioalveolar lavage fluid total cell counts, specifically reduced macrophages and neutrophils counts, but an increased presence of minority lymphocytes. TDF downregulated BLM-induced levels of Il1β, Il6, TNFα, and Tgfβ mRNA. Preventive treatment with TDF counteracted BLM-induced alveolar and bronchiolar cell damage. Male mice showed more severe symptoms after BLM administration for most parameters, and the preventive action of TDF was similar in both sexes. Preventive TDF administration partially counteracted BLM-induced acute lung injury. These findings support epidemiological observations suggesting a potential benefit of TDF as a prophylactic therapy against COVID-19, at least in HIV-infected patients.