Suppression of Human Neutrophil Functions by Tetracyclines

J Periodontal Res. 1991 Jan;26(1):52-8. doi: 10.1111/j.1600-0765.1991.tb01626.x.


Tetracycline inhibition of neutrophil-associated collagenolysis has been the focus of a number of investigations. Evidence has suggested that this inhibition results from the ability of this family of antimicrobial drugs to bind divalent cations such as Ca2+ and Zn2+, two cations that are required for full expression of activity of metalloproteinases such as collagenase and gelatinase. Data presented in this study demonstrate that tetracyclines can also inhibit neutrophil-mediated RBC lysis, superoxide anion synthesis, degranulation and migration. To some extent, tetracycline inhibition of neutrophil functions is mimicked by the Ca2+ binding agents, EDTA and TMB-8. However, Ca2+ enrichment restored full function to EDTA- and TMB-8-treated cells but not to tetracycline-treated neutrophils. This suggests that Ca2+ binding plays a role but is not the critical effect leading to tetracycline suppression of neutrophil functions. It has been suggested that tetracyclines can suppress leukocyte-associated tissue damage. Host tissues are protected from neutrophil-mediated damage by two mechanisms: 1. Neutrophil granule-associated enzymes are secreted in an inactive state; and, 2. tissues are protected from these enzymes by a potent inhibitor shield. Neutrophils can bypass these protective elements by activating enzymes and by destroying the shield through the synthesis of oxygen radicals. Therefore, tetracyclines may suppress neutrophil-mediated tissue damage by inhibiting their migration and degranulation and, potentially more importantly, by suppressing synthesis of oxygen radicals.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Adult
  • Calcium / metabolism
  • Cell Degranulation / drug effects
  • Cell Migration Inhibition
  • Doxycycline / pharmacology
  • Erythrocyte Membrane
  • Erythrocytes / physiology
  • Humans
  • Middle Aged
  • Minocycline / pharmacology
  • Neutrophils / drug effects*
  • Oxytetracycline / pharmacology
  • Superoxides / blood
  • Tetracycline / pharmacology*


  • Superoxides
  • Tetracycline
  • Minocycline
  • Doxycycline
  • Calcium
  • Oxytetracycline