Cytokine production in whole blood cell cultures of patients with rheumatoid arthritis

Objective-The measurement of cytokine production of activated lymphocytes and monocytes in the whole blood cell (WBC) culture system may provide a sensitive tool for evaluating the actual ongoing immune response of patients with rheumatoid arthritis (RA). Methods-Lipopolysaccharide (LPS) up to 250 pg/ml was used for the stimulation of monocytes for measuring the production of tumour necrosis factor alpha (TNF alpha), interleukin 6 (IL6) and IL12, while the anti-CD3 (1 mu g/ml) and anti-CD28 (5 mu g/ml) combination was used for T cell stimulation with the measuring of IL4 and interferon gamma (INF gamma) production. Twenty seven patients with RA and 23 healthy controls were studied. Results-The results showed a decreased IL6 (LPS stimulus 4-6 pg/ml) and IL12 (LPS stimulus 16-62 pg/ml) production in the RA patients. The maximal production of both cytokines was comparable with the normal controls. T cell stimulation showed a significant decreased INF gamma production in the RA patients. Conclusions-These findings obtained in the WBC culture system are highly suggestive for a decreased TH-1 derived cytokine production by a diminished IL12 production in RA patients. Another possibility is that both IL12 and INF gamma production in WBCs are inhibited by eventual circulating serum factors.