Methylprednisolone prevents tumour necrosis factor-α-dependent multinucleated giant cell formation

Abstract

Objectives: Granulomas contain multinucleated giant cells (MGCs), the function of which remains largely unknown. In patients with autoimmune granulomatous disease, the granulomas can be resolved during treatment with glucocorticosteroid (GCS). However, little is known about the influence of GCSs on the formation of MGCs. Methods: Monocytes isolated from buffy coats were stimulated with IFN-γ and Concanavalin A to form MGCs either in presence or absence of TNF-α, methylprednisolone (MP), adalimumab or human immunoglobulin G. The concentrations of IL-1β, IL-6, IL-10, IL-12p70 and TNF-α in the culture supernatants were measured after 18 h of stimulation. Results: MP, at a concentration of 0.1 μM, inhibited monocyte fusion (P < 0.05), and abrogated the formation of MGCs completely at higher concentrations. The production of IL-1β, IL-6 and TNF-α that accompanied MGC formation was reduced significantly by 10 μM MP. Recombinant TNF-α, at a concentration of 50 ng/ml, increased the number of formed MGCs and counteracted the inhibitory effect of 0.1 μM MP, while higher concentrations of MP still blocked MGC formation completely. Blockade of TNF-α with adalimumab within 16 h after stimulation significantly reduced the number MGCs formed (P < 0.05). Conclusion: MP inhibits the fusion of monocytes into MGCs, as well as the monocyte production of pro-inflammatory cytokines, which may be an important aspect of its beneficial effect in chronic granulomatous disorders. MCG formation can be promoted by TNF-α and inhibited by TNF-α blockade. © The Author 2010. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.