Systemic administration of enamel matrix derivative to lipopolysaccharide-challenged pigs: effects on the inflammatory response.
BACKGROUND
Periodontitis is the primary clinical indication for enamel matrix derivative (EMD). Recent investigations, showing that EMD inhibits the production of tumor necrosis factor-alpha (TNF-alpha) when added to human whole blood, indicate a novel role for EMD as a modulator of systemic inflammation. In the present study, we investigated the systemic effects of EMD in lipopolysaccharide (LPS)-challenged pigs.


METHODS
In a preparatory study, seven pigs received a prophylactic EMD bolus injection (5 mg/kg), followed by a continuous infusion (50 mg/kg/min). Thirty minutes later, a continuous infusion of LPS (1.7 mcg/kg/h) was started. An additional 12 pigs were randomized into two groups. Six of these animals were given the same treatment, except that EMD was administered 30 min after LPS. The remainder served as controls. The groups were compared according to organ injury and function, hemodynamics, and systemic markers of inflammation.


RESULTS
Prophylactic administration of EMD triggered transient hemodynamic instability in two of seven pigs. In the randomized pigs, no or only nonspecific changes were observed in biopsies from vital organs, independent of treatment. Enamel matrix derivative did not modify systemic TNF-alpha, interleukin (IL)-1 beta, or IL-6 concentrations.


CONCLUSIONS
In the formulation and dosages used, EMD did not modulate the inflammatory response. No true allergic or immunotoxic reactions were seen. To be usable for systemic application, a new formulation should be developed, or the active part of the protein(s) should be identified and produced in a soluble form designed for infusion. The potential of EMD as a systemic immune modulator is still unsettled.
Gundersen
R Yngvar
RY
Institute for Surgical Research, Rikshospitalet University Hospital, Rikshospitalet-Radiumhospitalet Medical Centre, Oslo, Norway. yngvar.gundersen@ffi.no
Ruud
Tom E
TE
Jørgensen
Pal F
PF
Scholz
Tim
T
Reinholt
Finn P
FP
Wang
Jacob E
JE
Lyngstadaas
Stale P
SP
Aasen
Ansgar O
AO
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003746:Dental Enamel Proteins / Q000494:pharmacology*; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000187:drug effects; D015850:Interleukin-6 / Q000276:immunology; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000276:immunology; D034421:Sus scrofa; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D003746:Dental Enamel Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C109069:enamel matrix proteins