High-dose, pulse intravenous methylprednisolone enhances Fc gamma receptor-mediated mononuclear phagocyte function in systemic lupus erythematosus.
The benefit of high-dose, pulse intravenous methylprednisolone (IVMP) for some patients with active lupus nephritis would appear paradoxical, since active nephritis is associated with profound abnormalities in Fc gamma receptor function, and several studies have demonstrated that glucocorticoids decrease monocyte Fc gamma receptor expression and phagocytic function. To resolve this paradox, we investigated the possibility that pulse IVMP might enhance monocyte Fc gamma receptor function in patients with systemic lupus erythematosus (SLE). Circulating immune complex (CIC) levels, Fc gamma receptor-mediated clearance, and Fc gamma receptor-dependent monocyte function were analyzed in 23 SLE patients before and after pulse IVMP (1 gm daily for 3 days). A biphasic response in CIC levels, determined by a staphylococcal protein A binding assay, was observed. Initially, CIC levels increased within 2-4 hours after the first dose of pulse IVMP and then decreased by 50% within 24-48 hours after the completion of therapy. Fc gamma receptor-mediated binding and phagocytosis of IgG-sensitized erythrocytes (EA) by monocytes in vitro were significantly enhanced 24 hours after the final dose of pulse IVMP (pre-IVMP versus post-IVMP 43 +/- 14% versus 53 +/- 12% EA rosettes, P less than 0.01; 3.00 +/- 1.04 versus 3.99 +/- 1.30 EA ingested/monocyte, P less than 0.01). In contrast, there was no change in the phagocytosis of an Fc gamma receptor-independent probe, neuraminidase-treated erythrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Salmon
J E
JE
Department of Medicine, New York Hospital-Cornell Medical Center, New York.
Kapur
S
S
Meryhew
N L
NL
Runquist
O A
OA
Kimberly
R P
RP
D000328:Adult; D000368:Aged; D000936:Antigen-Antibody Complex / Q000032:analysis; D000943:Antigens, Differentiation / Q000494:pharmacology*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000494:pharmacology; D008875:Middle Aged; D010586:Phagocytes / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects; D011961:Receptors, Fc / Q000494:pharmacology*; D017452:Receptors, IgG; D013997:Time Factors
D000936:Antigen-Antibody Complex; D000943:Antigens, Differentiation; D011961:Receptors, Fc; D017452:Receptors, IgG; D008775:Methylprednisolone