Abstract
Recombinant human interleukin-4 (rhIL-4) and rhIL-1α each produced a rapid down-modulation of tumour necrosis factor receptor (TNFR) on rheumatoid synovial fibroblasts (RSF) in vitro. This was associated with a staurosporine-resistant increase in p55 soluble TNFR levels, in culture media, suggesting that downmodulation was due to enhanced receptor shedding via a protein kinase C-independent mechanism. Pretreatment with rhIL-4 reduced the subsequent tumour necrosis factor α (TNFα) stimulation of prostaglandin E (PGE) and matrix metalloproteinase-3 (MMP-3) production by RSF. Thus, the potential anti-synovial monokine properties of rhIL-4 are not confined to inhibiting monokine production but also include the ability to interfere with their action on cells that constitute a substantial proportion of the rheumatoid synovium.
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Taylor, D.J. Interleukin-4 (IL-4) induces down-modulation and shedding of the p55 tumour necrosis factor receptor and inhibits TNF α's effect on rheumatoid synovial fibroblasts. Rheumatol Int 14, 21–25 (1994). https://doi.org/10.1007/BF00302667
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DOI: https://doi.org/10.1007/BF00302667