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

Abstract

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). 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 microgram/ml) and anti-CD28 (5 micrograms/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. The results showed a decreased IL6 (LPS stimulus 4-6 pg/ml) and IL-12 (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. 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.