PMID- 23381991
OWN - NLM
STAT- MEDLINE
DCOM- 20130514
LR  - 20211203
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 81
IP  - 4
DP  - 2013 Apr
TI  - The contraceptive depot medroxyprogesterone acetate impairs mycobacterial control 
      and inhibits cytokine secretion in mice infected with Mycobacterium tuberculosis.
PG  - 1234-44
LID - 10.1128/IAI.01189-12 [doi]
AB  - The contraceptive depot medroxyprogesterone acetate (DMPA), with progestin as the 
      single active compound, possesses selective glucocorticoid activity and can alter 
      the expression of glucocorticoid receptor-regulated genes. We therefore propose 
      that pharmacological doses of DMPA used for endocrine therapy could have 
      significant immune modulatory effects and impact on susceptibility to, as well as 
      clinical manifestation and outcome of, infectious diseases. We investigated the 
      effect of contraceptive doses of DMPA in two different murine Mycobacterium 
      tuberculosis models. Multiplex bead array analysis revealed that DMPA altered 
      serum cytokine levels of tumor necrosis factor alpha (TNF-alpha), granulocyte 
      colony-stimulating factor (G-CSF), and interleukin 10 (IL-10) in C57BL/6 mice and 
      gamma interferon (IFN-gamma) in BALB/c mice. DMPA also suppressed antigen-specific 
      production of TNF-alpha, G-CSF, IL-10, and IL-6 and induced the production of IP-10 
      in C57BL/6 mice. In BALB/c mice, DMPA altered the antigen-specific secretion of 
      IFN-gamma, IL-17, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, 
      and monocyte chemotactic protein 1 (MCP-1). Furthermore, we show that C57BL/6 
      mice treated with doses of DMPA, which result in serum concentrations similar to 
      those observed in contraceptive users, have a significantly higher bacterial load 
      in their lungs. Our data show for the first time that DMPA impacts tuberculosis 
      (TB) disease severity in a mouse model and that the effects of this contraceptive 
      are not confined to infections of the genital tract. This could have major 
      implications for the contraceptive policies not only in developing countries like 
      South Africa but also worldwide.
FAU - Kleynhans, Leanie
AU  - Kleynhans L
AD  - DST/NRF Centre of Excellence for Biomedical TB Research/MRC Centre for Molecular 
      and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty 
      of Medicine and Health Sciences, Stellenbosch University, Cape Town, South 
      Africa.
FAU - Du Plessis, Nelita
AU  - Du Plessis N
FAU - Allie, Nasiema
AU  - Allie N
FAU - Jacobs, Muazzam
AU  - Jacobs M
FAU - Kidd, Martin
AU  - Kidd M
FAU - van Helden, Paul D
AU  - van Helden PD
FAU - Walzl, Gerhard
AU  - Walzl G
FAU - Ronacher, Katharina
AU  - Ronacher K
LA  - eng
GR  - U2R TW007370/TW/FIC NIH HHS/United States
GR  - 1U2RTW007370/3/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130204
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Contraceptive Agents)
RN  - 0 (Cytokines)
RN  - 0 (Immunologic Factors)
RN  - C2QI4IOI2G (Medroxyprogesterone Acetate)
SB  - IM
MH  - Animals
MH  - Contraceptive Agents/*administration & dosage/adverse effects
MH  - Cytokines/*blood/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Immunologic Factors/*administration & dosage/adverse effects
MH  - *Immunosuppression Therapy
MH  - Medroxyprogesterone Acetate/*administration & dosage/adverse effects
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mycobacterium tuberculosis/*immunology
MH  - Tuberculosis/*immunology
PMC - PMC3639598
EDAT- 2013/02/06 06:00
MHDA- 2013/05/15 06:00
PMCR- 2013/10/01
CRDT- 2013/02/06 06:00
PHST- 2013/02/06 06:00 [entrez]
PHST- 2013/02/06 06:00 [pubmed]
PHST- 2013/05/15 06:00 [medline]
PHST- 2013/10/01 00:00 [pmc-release]
AID - IAI.01189-12 [pii]
AID - 01189-12 [pii]
AID - 10.1128/IAI.01189-12 [doi]
PST - ppublish
SO  - Infect Immun. 2013 Apr;81(4):1234-44. doi: 10.1128/IAI.01189-12. Epub 2013 Feb 4.