Anti-tumor necrosis factor-alpha treatment activates Borrelia burgdorferi spirochetes 4 weeks after ceftriaxone treatment in C3H/He mice.
BACKGROUND
The effect of anti-tumor necrosis factor (TNF)-alpha treatment in Borrelia burgdorferi-infected and ceftriaxone-treated C3H/He mice was evaluated.


METHODS
Mice were infected with B. garinii A218 or B. burgdorferi sensu stricto N40. At 2 weeks of infection, one group was treated simultaneously with ceftriaxone and anti-TNF-alpha, whereas another received ceftriaxone at 2 weeks and anti-TNF-alpha 4 weeks later. One group received ceftriaxone treatment only. Infected and noninfected control groups were sham treated.


RESULTS
At 14 weeks of infection, B. burgdorferi could not be detected by cultivation or by polymerase chain reaction in tissue samples of any mouse treated with ceftriaxone only. However, spirochetes grew from the tissue samples of one-third of the mice treated with anti-TNF-alpha simultaneously or 4 weeks after ceftriaxone. These activated spirochetes showed ceftriaxone sensitivity rates, plasmid profiles, and virulence rates similar to those of bacteria used to infect the mice. All infected control mice and mice given anti-TNF-alpha only were culture positive.


CONCLUSIONS
This report shows that, after ceftriaxone treatment for 5 days, a portion of B. burgdorferi-infected mice still have live spirochetes in their body, which are activated by anti-TNF-alpha treatment.
Yrjänäinen
Heta
H
Department of Medical Microbiology, University of Turku, Turku, 20520, Finland. heta.yrjanainen@utu.fi
Hytönen
Jukka
J
Song
Xiao-yu R
XY
Oksi
Jarmo
J
Hartiala
Kaija
K
Viljanen
Matti K
MK
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000906:Antibodies / Q000627:therapeutic use; D025065:Borrelia burgdorferi / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology*; D015748:Borrelia burgdorferi Group / Q000187:drug effects / Q000302:isolation & purification; D002443:Ceftriaxone / Q000009:adverse effects / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000627:therapeutic use; D007592:Joint Diseases / Q000139:chemically induced / Q000517:prevention & control; D007700:Kinetics; D008193:Lyme Disease / Q000188:drug therapy*; D051379:Mice; D008809:Mice, Inbred C3H; D051381:Rats; D013144:Spirochaetales / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
D000900:Anti-Bacterial Agents; D000906:Antibodies; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D002443:Ceftriaxone