Prednisolone reduces experimental arthritis, and inflammatory tissue destruction in SCID mice infected with Borrelia burgdorferi.
Glucocorticosteroids (GC) are widely used as anti-inflammatory agents. The effects of Prednisolone on the development of Borrelia (B.) burgdorferi-induced clinical arthritis and organ inflammation was studied in severe combined immunodeficiency (SCID) mice. The drug was administered orally at a dose of 3, 10 and 30 mg/kg, starting shortly before experimental infection of the mice. A dose dependent inhibition of arthritic joint swelling was observed. Full protection was obtained with 30 mg/kg until 21 days after infection, subsequently, mild joint swelling developed but progression and severity of the disease was considerably less than in the other treated as well as in the untreated mice. Inhibition of clinical arthritis coincided with reduction of inflammatory cell infiltration in the joints, liver and muscle. Prednisolone was ineffective when application was initiated after arthritis was fully developed, i.e., 22 days after infection. Since the activated endothelium plays a critical role in development of inflammatory lesions, the expression of the cellular adhesion molecules (CAMs) E-selectin, P-selectin, ICAM-1 and VCAM-1 was determined in vitro using the bEnd3 endothelial cell line. Stimulation with a sonicated B. burgdorferi preparation in the presence of the water-soluble compound Prednisolone-21-hemisuccinate considerably reduced expression of ICAM-1, and marginally also of E-selectin, whereas the level of P-selectin and VCAM-1 remained unaltered. Thus, downregulation of ICAM-1 might be a critical factor in Prednisolone-mediated inhibition of B. burgdorferi-induced inflammation; the flare up of the disease after the initial protection indicates that additional therapy, e.g. with antibiotics, is necessary.
Hurtenbach
U
U
Max Planck Institut für Immunbiologie, Freiburg, Germany.
Böggemeyer
E
E
Stehle
T
T
Museteanu
C
C
Del Pozo
E
E
Simon
M M
MM
D000818:Animals; D001170:Arthritis, Infectious / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D015748:Borrelia burgdorferi Group / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000187:drug effects; D005260:Female; D006390:Hemangioendothelioma; D007596:Joints / Q000473:pathology; D008193:Lyme Disease / Q000150:complications / Q000473:pathology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011239:Prednisolone / Q000627:therapeutic use*; D013643:Tarsus, Animal; D013977:Tibia / Q000473:pathology; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D011239:Prednisolone