CONTRASTING LEVELS OF IN-VITRO CYTOKINE PRODUCTION BY RHEUMATOID SYNOVIAL TISSUES DEMONSTRATING DIFFERENT PATTERNS OF MONONUCLEAR CELL INFILTRATION

Synovial membrane samples obtained at knee arthroplasty from 22 patien ts with rheumatoid arthritis (RA) were characterized histologically. T wo groups were identified. Tissue samples from 15 patients demonstrate d multiple focal lymphoid aggregates of mononuclear cells (group A). S amples from the remaining seven patients demonstrated diffuse mononucl ear cell infiltration (group B). Samples of each synovial membrane (0- 25 g) were cultured for cytokine production. The highest levels of IL- 1beta and IL-6 were produced by group A tissues: 19.1 +/- 19.6 ng/ml I L-1beta (mean +/- s.d.) and 264.4 +/- 301.9 ng/ml IL-6, versus 3.8 +/- 6.6 ng/ml and 54.7 +/- 42-6 ng/ml respectively. Small quantities of I L-2 and IL-4 were measured in both groups: the levels of IL-2 in group A cultures were highest (P = 0.04). Moreover, using MoAbs, the most i ntense cytokine staining in the tissues was detected in group A. Simil ar total numbers of each cell subpopulation and similar quantities of immunoglobulin and rheumatoid factor synthesis were measured in both g roups . It is suggested that the presence of multiple focal lymphoid a ggregates associated with higher levels of cytokine production observe d in group A represent a greater degree of immunological activation, a nd may represent a subgroup of patients with a greater potential for a rticular destruction.