Inflammatory cytokine production by immunological and foreign body multinucleated giant cells

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Abstract
Multinucleated giant cells (MGC) are a common feature of granulomas. The mechanism of their formation has been studied extensively, but their function has not been completely characterized. A new method for the in vivo production of MGC was developed involving subcutaneous injection of microscopic nitrocellulose particles with adsorbed mycobacterial antigens into the footpads of sensitized BALB/c mice (immune [I]-MGC), or by nitrocellulose administration to non-sensitized mice (foreign body [FB]-MGC). The development of granulomas with a highly enriched MGC population was observed 2 weeks after the nitrocellulose injection. MGC were larger with a greater number of nuclei in I-MGC than in FB-MGC. From days 7–28 after nitrocellulose administration, the production of interleukin-1α (IL-1α) and tumour necrosis factor-α (TNF-α) was demonstrated in both MGC types by in situ reverse transcription–polymerase chain reaction (RT–PCR) and immunohistochemistry. After 2 months, the MGC had ceased production of IL-1α and TNF-α, but the expression of transforming growth factor-β (TGF-β) was very high, occurring together with extensive fibrosis. These results suggest that MGC are an active source of inflammatory cytokines, which can contribute to the initiation, maintenance and down-regulation of granulomatous inflammation induced by immunological and inert substances.