cholecalciferol and Pneumonia--Pneumocystis

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.

Topics: Albumins; Animals; Antifungal Agents; Calcium; CD11b Antigen; Cholecalciferol; Dietary Supplements; Drug Therapy, Combination; Female; L-Lactate Dehydrogenase; Lung; Macrophages, Alveolar; Mice, Inbred C57BL; Pneumocystis; Pneumonia, Pneumocystis; Primaquine; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Cholecalciferol; Humans; Infant; Male; Mediastinal Emphysema; Myocarditis; Pharyngitis; Pneumonia, Pneumocystis; Pneumothorax