Minocycline delays but does not attenuate the course of experimental autoimmune encephalomyelitis in Streptococcus pneumoniae-infected mice.
OBJECTIVE
Experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), can be aggravated by a mild Streptococcus pneumoniae infection. This study was performed to assess whether treatment with antibiotics inhibiting bacterial protein synthesis reduces the detrimental effect of infection on the course of EAE.


METHODS
In vitro, release of proinflammatory pneumococcal products was studied by enzyme immunoassay and western blot. Seven days after induction of EAE (prior to the onset of symptoms) mice were infected intraperitoneally with S. pneumoniae and treated either with the inhibitors of bacterial protein synthesis minocycline or rifampicin, or with the beta-lactam ceftriaxone.


RESULTS
During bacterial killing in vitro, minocycline and rifampicin released lower quantities of proinflammatory bacterial products from S. pneumoniae than ceftriaxone. Mice treated with minocycline developed symptoms of EAE 1 day later than mice treated with ceftriaxone. Neither minocycline nor rifampicin therapy, however, reduced the severity of EAE in comparison with ceftriaxone treatment.


CONCLUSIONS
Although statistically significant (P = 0.04), a delay of 1 day in the onset of symptoms of EAE after minocycline treatment is of minor clinical relevance. These data do not support the hypothesis of superiority of a bacterial protein synthesis inhibitor over a beta-lactam antibiotic for the treatment of concomitant infections during the latent phase of EAE or MS.
Herrmann
Isabel
I
Department of Neurology, Georg August University, D-37075 Göttingen, Germany.
Kellert
Markus
M
Spreer
Annette
A
Gerber
Joachim
J
Eiffert
Helmut
H
Prinz
Marco
M
Nau
Roland
R
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002443:Ceftriaxone / Q000097:blood / Q000627:therapeutic use; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications*; D005260:Female; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D008911:Minocycline / Q000097:blood / Q000627:therapeutic use*; D011008:Pneumococcal Infections / Q000150:complications / Q000188:drug therapy*; D012293:Rifampin / Q000494:pharmacology; D013682:Teichoic Acids / Q000378:metabolism
D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D013682:Teichoic Acids; C009900:lipoteichoic acid; D002443:Ceftriaxone; D008911:Minocycline; D012293:Rifampin