Effect of aggregated immunoglobulins on mononuclear cell protein production in rheumatoid arthritis

The synthesis and secretion of proteins, especially interleukin 1 (IL-1), by mononuclear cells from patients with rheumatoid arthritis (RA) in response to heat-aggregated IgG (HAGG) has been investigated. Mononuclear cells were labeled with 35S-methionine during 1 hr of HAGG stimulation, and the intracellular and extracellular protein content was measured and compared by fluorography. HAGG dramatically accelerated protein release into the medium. This was observed in both normal and RA mononuclear cells but was much more marked with the latter. The phenomenon was correlated with the release of a IL-1 activity measurable in the thymocyte proliferation assay with a more pronounced labeling in the extracellular medium of a 14-kDa band not detectable in the intracellular pattern. Partially purified proteins between 14-20 kDa recovered by transblotting also stimulated thymocyte proliferation. These results therefore suggest a particular sensitivity of RA mononuclear cells to HAGG, resulting in a very rapid de novo synthesis and an accelerated secretion rate of IL-1.