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.) burgd orferi-induced clinical arthritis and organ inflammation was studied i n severe combined immunodeficiency (SCID) mice. The drug was administe red orally at a dose of 3, 10 and 30 mg/kg, starting shortly before ex perimental infection of the mice. A dose dependent inhibition of arthr itic joint swelling was observed. Full protection was obtained with 30 mg/kg until 21 days after infection, subsequently, mild joint swellin g developed but progression and severity of the disease was considerab ly less than in the other treated as well as in the untreated mice. In hibition of clinical arthritis coincided with reduction of inflammator y cell infiltration in the joints, liver and muscle. Prednisolone was ineffective when application was initiated after arthritis was fully d eveloped, i.e. 22 days after infection. Since the activated endotheliu m plays a critical role in development of inflammatory lesions, the ex pression of the cellular adhesion molecules (CAMs) E-selectin, P-selec tin, ICAM-1 and VCAM-1 was determined in vitro using the bEnd3 endothe lial cell line. Stimulation with a sonicated B. burgdorferi preparatio n in the presence of the water-soluble compound Prednisolone-21-hemisu ccinate considerably reduced expression of ICAM-1, and marginally also of E-selectin, whereas the level of P-selectin and VCAM-1 remained un altered. Thus, downregulation of ICAM-1 might be a critical factor in Prednisolone-mediated inhibition of B. burgdorferi-induced inflammatio n; the flare up of the disease after the initial protection indicates that additional therapy, e.g. with antibiotics, is necessary. Copyrigh t (C) 1996 International Society for Immunopharmacology