High-molecular-weight PEG precipitates from synovial fluid induce more TNF-α than those from serum of RA patients, which is in contrast to patients with other inflammatory arthritides

Background

We have earlier shown that polyethylene glycol (PEG) precipitates from sera of active SLE patients can induce monokine production, possibly through immune complexes.

Objective

We have now investigated monokine production induced by PEG precipitates from arthritis patients.

Methods

Paired synovial fluid (SF) and serum samples from 26 RA patients and 20 patients with other inflammatory arthritides were subjected to combined PEG precipitation and purification. The IgG content was determined by ELISA. Precipitates were added to peripheral blood mononuclear cell (PBMC) cultures, and supernatant levels of TNF-α and IL-10 determined by ELISA after 20 hours.

Results

In both the investigated PBMC donors, the highest median values of TNF-α were found in SF-PEG cultures. In one of the PBMC donors, this difference was significant in paired analysis for all patients and for the RA group only, but not for non-RA patients only. The correlation between the TNF-α and IL-10 production was higher for RA than for non-RA patients, and higher for SF than for serum precipitates. No correlation was noted between the IgG content of the precipitates and cytokine levels.

Conclusion

In this preliminary study, PEG precipitates from RA SF induced higher production of TNF-α than did corresponding serum precipitates, possibly through stimulation by immune complexes in SF. Since no correlation was observed between the IgG content and cytokine induction, it is likely that immune-complex composition rather than the IgG content of the precipitates determines the cytokine response.