Vitamin D effect on invasive aspergillosis

Ref ID: 19518

Author:

C Sirivoranankul1,2*, M Martinez1, V Chen1, KV Clemons1,3, DA Stevens1,3

Author address:

1California Institute for Medical Research, San Jose, USA
2University of California, Los Angeles, Los Angeles, USA
3Stanford University Medical School, Palo Alto, USA

Full conference title:

6th Advances Against Aspergillosis 2014

Abstract:

Purpose:
The D receptor and D metabolizing enzymes are expressed by immune cells. Interest in the effect
of D on aspergillosis stems from the demonstrated D effects, in humans and mice, on T & B cells,
including Tregs, cytokine production, macrophages, antigen-presenting cells, antimicrobial peptides;
Toll-like, Dectin-1 and mannose receptors; & microbial killing, all relevant to the importance of
Th1/Th2 and effector phagocytes in aspergillosis. Favorable D effects have been shown in tuberculosis.
D deficiency increases Th2 responses to A. fumigatus (Af), and D suppresses Th2 responses to Af in
cystic fibrosis-ABPA. Another issue is whether D could modulate the pro-inflammatory effects of
amphotericin B (AmB) therapy in aspergillosis.
Method:
Groups of 10 five-week-old female CD1 mice were infected intravenously (IV) with (3-8) x 106 Af
condida. In 6 experiments, doses of 0.08, 2 or 4 mcg/kg calcitriol (active form of D) were given
intraperitoneally (IP), and/or AmB deoxycholate 0.4, 0.8, 1.2, 1.8, 3.3, or 4.5 mg/kg IP or 0.8 or
1.2 mg/kg IV. Calcitriol doses were selected to range from doses used in humans, up to those below
doses shown to decalcify murine bones. Doses of calcitriol, AmB (or control diluents) were given
5 times each, on alternate days (QOD), to minimize drug-drug interactions (in single experiments
calcitriol was also studied daily x 10 or QOD x 4, or AmB daily x 10 or QOD x 3). D treatment
began on the day of challenge, and survival was followed for 10 days. In 1 experiment, posaconazole
5mg/kg PO daily was also studied +/- calcitriol.
Results:
In no experiments did any dose of calcitriol alone significantly worsen or enhance survival or affect
residual CFU in survivors. Calcitriol also did not affect antifungal efficacy. In a representative
experiment, 0.8 or 1.2 mg/kg AmB IV +/- 2 mcg/kg calcitriol increased survival p8804;0.01, but the
AmB regimens with calcitriol were not different (p=0.2-0.8) than without calcitriol, and calcitriol
alone was identical to controls.
Conclusion:
In this model of disseminated invasive aspergillosis, calcitriol did not affect outcome nor influence
antifungal efficacy. Studies of other aspergillosis models would be of interest.

Abstract Number: 46

Conference Year: 2014

Link to conference website: http://www.AAA2014.org

New link: NULL

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