Volume 6 Supplement 1
Immune complexes from RA patients induce FcγRII-dependent and RF-correlated TNF-α and IL-8 production from healthy PBMC
© The Author(s) 2004
Received: 16 January 2004
Published: 24 February 2004
Immune complexes (IC) induce production of cytokines from mononuclear cells via Fcγ-receptors. We investigated whether polyethylene glycol (PEG)-precipitated IC from serum and synovial fluid (SF) from rheumatoid arthritis (RA) patients can induce production of proinflammatory cytokines.
In one study we compared sera and SF from 15 RA patients and 15 healthy control sera. In a second study we used paired sera and SF from 32 RA patients, 66% of which were rheumatoid factor (RF) positive. The precipitates where diluted to the original volume in PBS before 10% were added to serum-free PBMC cultures from two healthy blood donors. After 20 hours TNF-α and IL-8 levels were measured using ELISA. In separate cell culture experiments FcγRII and FcγRIII were blocked. RF in serum was determined by nephelometry and IgG levels in precipitates were measured using ELISA.
We found a correlation between TNF-α induced by PEG precipitates from RA SF and RF levels in sera. Using the normal ELISA, PEG precipitates were shown to contain some TNF-α but no IL-8, using both whole and F(ab')2 anti-TNF-α antibody ELISA systems. TNF-α levels induced by SF precipitates, but not by serum precipitates, correlated with number of swollen and tender joints at the time of sampling. Blockade of FcγRII partly inhibited the TNF-α production in cultures stimulated with precipitated IC, whereas blockade of FcγRIII did not show any inhibitory effects.