High‐Dose, pulse intravenous methylprednisolone enhances fcγ receptor–mediated mononuclear phagocyte function in systemic lupus erythematosus

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Abstract
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 Fcγ receptor function, and several studies have demonstrated that glucocorticoids decrease monocyte Fcγ receptor expression and phagocytic function. To resolve this paradox, we investigated the possibility that pulse IVMP might enhance monocyte Fcγ receptor function in patients with systemic lupus erythematosus (SLE). Circulating immune complex (CIC) levels, Fcγ receptor–mediated clearance, and Fcγ 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. Fcγ 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 < 0.01; 3.00 ± 1.04 versus 3.99 ± 1.30 EA ingested/monocyte, P < 0.01). In contrast, there was no change in the phagocytosis of an Fcγ receptor–independent probe, neuraminidasetreated erythrocytes. This enhancement of monocyte Fcγ receptor function may reflect a synergism between glucocorticoids and a suitably primed mononuclear phagocyte in SLE. Glucocorticoid-induced augmentation of Fcγ receptor function in the presence of γ-interferon, which may be elevated in SLE, has been shown. The enhancement of monocyte Fcγ receptor function that we observed may contribute to the therapeutic efficacy of pulse IVMP in lupus nephritis.