Therapeutic studies of the combination of deoxyspergualin and prednisolone in MRL/lpr mice with advanced lupus-like disease.

Abstract

Female MRL/lpr mice develop lesions closely resembling human systemic lupus, and therefore can serve as modelsin order to examinethe efficacy of immunosuppressive agents. The present study was designed to evaluate the efficacy of the combination of deoxyspergualin with prednisolone compared with each alone in 1 3-week-old female MRL/lpr mice. After the onset oflymphadenopathy, splenomegaly, and the elevation of plasma autoantibodies, deoxyspergualin alone or prednisolone alone was effective. Animmunosuppressive regimen of deoxyspergualin combined with prednisolone was demonstrated to be superior to each single therapy concerning the amelioration of advanced disease in the MRL/lpr mice without increasing toxicity.

HSC70 blockade by the therapeutic peptide P140 affects autophagic processes and endogenous MHCII presentation in murine lupus

“…B cells, T cells (including γδT cells and DN T cells) and granulocytes/monocytes were affected. In CBA/J control mice, however, even an overdosage of P140 did not produce any observable effect while, in contrast, the glucocorticoid prednisolone, which is active in MRL/lpr mice,9 and immunosuppressant ciclosporin A induced a decrease of PBL counts in both CBA/J and MRL/lpr mice (figure 1F). Peripheral B and T cells from non-treated MRL/lpr mice and remaining peripheral B and T cells from P140-treated mice responded equally well ex vivo to B-cell mitogen and slightly less well (p=0.024) to T-cell mitogen (figure 1G).…”

Deoxyspergualin: A New Immunosuppressive Drug for the Treatment of Auto-Immune Disease

“…An impor tant aspect of deoxyspergualin action is its ability to sup press the established disease process in many of these models [24,25,27,30,34,36,38]. Combinations of deox yspergualin with other immunosuppressive drugs have provided greater protection than monotherapies in sever al models.…”

“…best-studied models of auto-immune disease are MRLIpr/lpr and (NZBxNZW) F| mice which spontaneously develop lymphadenopathy, auto-antibody production, and deposition of immune complexes in glomeruli and joints, leading to aggressive crescentic glomerulonephritis and arthritis. Deoxyspergualin treatment suppresses dis ease development in both mouse strains and can also reverse established glomerulonephritis in these animalsbeing more effective than méthylprednisolone in inter vention studies [23][24][25][26][27], In addition, the use of low-dose deoxyspergualin plus méthylprednisolone is more effec tive than either agent alone at preventing onset of auto immune disease in these animals [27], A detailed study of deoxyspergualin action has also been made in a model of Goodpasture's syndrome in duced by injection of rabbit antiglomerular basement membrane serum into antigen-primed rats [28,29]. While daily deoxyspergualin treatment (5 mg/kg) was un able to prevent neutrophil-mediated renal and lung inju ry during the first 24 h, the drug (1) did prevent a fall in creatinine clearance; (2) suppressed proteinuria; (3) pre vented glomerular necrosis, fibrosis, and crescent forma tion; (4) abrogated tubulo-interstitial damage, and (5) prevented the formation of pulmonary granuloma tous lesions.…”