Inflammatory response to chlorhexidine, minocycline HCl and doxycycline HCl in an in vivo mouse model.
OBJECTIVE
To examine the effect of locally delivered antimicrobial drugs on the inflammatory response in an in vivo mouse chamber model.


METHODS
Two weeks following chamber implantation, 24 BALB/c mice, in the experimental group, were given an intra-chamber challenge of heat-killed Porphyromonas gingivalis, followed immediately by injection of the specific antimicrobial drug: 2000 microg/ml chlorhexidine (CHX); 1500 microg/ml minocycline HCl;and 1500 microg/ml doxycycline HCl (concentrations achieved in the periodontal pocket with commercial controlled-release delivery systems). A second group of 24 animals received only the antimicrobial treatment without P. gingivalis challenge. Intra-chamber exudates were sampled at 2 and 24 h following the challenge, and leucocytes, TNFalpha, IFNgamma and IL-10 were evaluated.


RESULTS
At 2 h, minocycline HCl induced high levels of IL-10, TNFalpha and IFNgamma, while CHX reduced the levels of TNFalpha and IFNgamma. By 24 h, these responses were attenuated. Following bacterial challenge, the antibacterial agents attenuated the inflammatory process, each in its own fashion.


CONCLUSIONS
Antibacterial agents applied locally have the ability to induce an inflammatory response. They also modify the inflammatory response to P. gingivalis independent of their antimicrobial effect. CHX and doxycycline HCl appear to have the most marked anti-inflammatory effect.
Houri-Haddad
Yael
Y
Department of Periodontology, Faculty of Dental Medicine, Hadassah and Hebrew University Medical Centers, Jerusalem, Israel.
Halabi
Amal
A
Soskolne
Wilfred Aubrey
WA
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000891:Anti-Infective Agents, Local / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D002710:Chlorhexidine / Q000627:therapeutic use*; D015194:Diffusion Chambers, Culture; D004195:Disease Models, Animal; D004318:Doxycycline / Q000627:therapeutic use*; D005122:Exudates and Transudates; D005260:Female; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008911:Minocycline / Q000627:therapeutic use*; D016966:Porphyromonas gingivalis / Q000276:immunology; D040521:Subcutaneous Tissue / Q000382:microbiology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000900:Anti-Bacterial Agents; D000891:Anti-Infective Agents, Local; D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D008911:Minocycline; D004318:Doxycycline; D002710:Chlorhexidine