Subantimicrobial-dose doxycycline treatment increases serum cholesterol efflux capacity from macrophages

Aino Salminen, Pirkko J. Pussinen, Jeffrey B. Payne, Julie A. Stoner, Matti Jauhiainen, Lorne M. Golub, Hsi Ming Lee, David M. Thompson, Timo Sorsa

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Objective: Subantimicrobial-dose doxycycline (SDD) treatment has been reported to reduce the severity of chronic inflammation and to increase serum high-density lipoprotein cholesterol. In a double-blind, placebo-controlled clinical trial, we determined whether SDD affects the ability of serum to facilitate cholesterol removal from macrophages. Methods: Forty-five postmenopausal osteopenic women with periodontitis were randomly assigned to take placebo (n = 26) or doxycycline hyclate (20 mg, n = 19) tablets twice daily for 2 years. Serum samples were collected at baseline, 1-, and 2-year appointments. The cholesterol efflux capacity of serum from cultured human macrophages (THP-1) was measured. Results: SDD subjects demonstrated a significant increase in serum-mediated cholesterol efflux from macrophages at both time points compared to baseline (p < 0.04 for each). Mean cholesterol efflux levels over the first year of follow-up were 3.0 percentage points (unit change) higher among SDD subjects compared to placebo subjects (p = 0.010), while there was no significant difference in 2-year changes. There were no significant differences in the changes of apolipoprotein A-I, apolipoprotein A-II, or serum amyloid A levels between the groups. Conclusions: Our results suggest that SDD treatment may reduce the risk of cardiovascular disease in this patient group by increasing the cholesterol efflux capacity of serum.

Original languageEnglish (US)
Pages (from-to)711-720
Number of pages10
JournalInflammation Research
Issue number7
StatePublished - Jul 2013


  • Atherosclerosis
  • Clinical trials
  • Inflammation
  • Lipids
  • Macrophages

ASJC Scopus subject areas

  • Immunology
  • Pharmacology


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