Lei, Guang-ShengZhang, ChenZimmerman, Michelle K.Lee, Chao-Hung2017-05-182017-05-182016-03Lei, G.-S., Zhang, C., Zimmerman, M. K., & Lee, C.-H. (2016). Vitamin D as Supplemental Therapy for Pneumocystis Pneumonia. Antimicrobial Agents and Chemotherapy, 60(3), 1289–1297. http://doi.org/10.1128/AAC.02607-15https://hdl.handle.net/1805/12622The combination of all-trans retinoic acid (ATRA) and primaquine (PMQ) has been shown to be effective for therapy of Pneumocystis pneumonia (PCP). Since a high concentration of ATRA has significant adverse effects, the possibility that vitamin D can be used to replace ATRA for PCP therapy was investigated. C57BL/6 mice were immunosuppressed by depleting CD4+ cells and infected with Pneumocystis murina 1 week after initiation of immunosuppression. Three weeks after infection, the mice were treated orally for 3 weeks with vitamin D3 (VitD3) alone, PMQ alone, a combination of VitD3 and PMQ (VitD3-PMQ), or a combination of trimethoprim and sulfamethoxazole (TMP-SMX). Results showed that VitD3 (300 IU/kg/day) had a synergistic effect with PMQ (5 mg/kg/day) for therapy of PCP. Flow cytometric studies showed that this VitD3-PMQ combination recovered the CD11blow CD11chigh alveolar macrophage population in mice with PCP as effectively as TMP-SMX. The VitD3-PMQ combination also reduced the massive infiltration of inflammatory cells into the lungs and the severity of lung damage. VitD3 was also shown to reduce the dose of TMP-SMX required for effective treatment of PCP. Taken together, results of this study suggest that a VitD3-PMQ combination can be used as an alternative therapy for PCP.en-USPublisher PolicyPneumonia, PneumocystisTrimethoprim, Sulfamethoxazole Drug CombinationCholecalciferolLungArticle