Mechanisms of action of vitamin D as supplemental therapy for Pneumocystis pneumonia

Guang Sheng Lei, Chen Zhang, Bi Hua Cheng, Chao-Hung Lee

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The combination of trimethoprim and sulfamethoxazole (TMP-SMX) is the most effective regimen for therapy of Pneumocystis pneumonia (PCP). As many patients with PCP are allergic or do not respond to it, efforts have been devoted to develop alternative therapies for PCP. We have found that the combination of vitamin D3 (VitD3) (300 IU/kg/day) and primaquine (PMQ) (5 mg/kg/day) was as effective as TMP-SMX for therapy of PCP. In this study, we investigated the mechanisms by which vitamin D enhances the efficacy of PMQ. C57BL/6 mice were immunosuppressed by CD4+ cell depletion, infected with Pneumocystis murina for 8 weeks, and then treated for 9 days with the combination of VitD3 and PMQ (VitD3-PMQ) or with TMP-SMX or PMQ to serve as controls. The results showed that vitamin D supplementation increased the number of CD11c+ cells, suppressed the production of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], gamma interferon [IFN-γ], and interleukin-6 [IL-6]) and inducible nitric oxide synthase (iNOS), and enhanced the expression of genes related to antioxidation (glutathione reductase and glutamate-cysteine ligase modifier subunit), antimicrobial peptides (cathelicidin), and autophagy (ATG5 and beclin-1). These results suggest that the main action of vitamin D is enhancing the ability of the host to defend against Pneumocystis infection.

Original languageEnglish (US)
Article numbere01226
JournalAntimicrobial Agents and Chemotherapy
Volume61
Issue number10
DOIs
StatePublished - Oct 1 2017

Fingerprint

Primaquine
Pneumocystis Pneumonia
Vitamin D
Sulfamethoxazole Drug Combination Trimethoprim
Cholecalciferol
Pneumocystis
Pneumocystis Infections
Glutamate-Cysteine Ligase
Murinae
Glutathione Reductase
Autophagy
Nitric Oxide Synthase Type II
Therapeutics
Complementary Therapies
Inbred C57BL Mouse
Interferon-alpha
Interferon-gamma
Interleukin-6
Tumor Necrosis Factor-alpha
Cell Count

Keywords

  • Alveolar macrophages
  • Pneumocystis pneumonia
  • Vitamin D

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Mechanisms of action of vitamin D as supplemental therapy for Pneumocystis pneumonia. / Lei, Guang Sheng; Zhang, Chen; Cheng, Bi Hua; Lee, Chao-Hung.

In: Antimicrobial Agents and Chemotherapy, Vol. 61, No. 10, e01226, 01.10.2017.

Research output: Contribution to journalArticle

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