title: Vitamin D as Supplemental Therapy for Pneumocystis Pneumonia.
abstract: The 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 CD11b(low) CD11c(high) 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Guang-Sheng
authors.initials: GS
authors.lastname: Lei
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Zimmerman
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA chlee@iupui.edu.
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D039481:CD11b Antigen / Q000378:metabolism; D002118:Calcium / Q000097:blood; D002762:Cholecalciferol / Q000097:blood / Q000494:pharmacology*; D019587:Dietary Supplements; D004359:Drug Therapy, Combination; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects; D008810:Mice, Inbred C57BL; D011010:Pneumocystis / Q000472:pathogenicity; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011319:Primaquine / Q000494:pharmacology*; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000418:Albumins; D000935:Antifungal Agents; D039481:CD11b Antigen; D002762:Cholecalciferol; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D007770:L-Lactate Dehydrogenase; D011319:Primaquine; D002118:Calcium