Vitamin D as Supplemental Therapy for Pneumocystis pneumonia.
Antimicrob Agents Chemother. 2015 Dec 14;
Authors: Lei GS, Zhang C, Zimmerman MK, Lee CH
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 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 one week after initiation of immunosuppression. Three weeks after infection, the mice were treated orally for three weeks with vitamin D3 (VitD3) alone, PMQ alone, combination of VitD3 and PMQ (VitD3-PMQ), or 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 VitD3-PMQ combination can be used as an alternative therapy for PcP.
PMID: 26666941 [PubMed - as supplied by publisher]