Abstract

The outcome of inflammatory reactions is thought to depend upon the balance between the production of proinflammatory, immunoactivating cytokines, such as interleukin (IL)-1a and b, IL-6 and tumour necrosis factor a (TNFa), and anti-inflammatory cytokines and cytokineantagonists such as IL-1 receptor antagonist (IL-1ra), soluble TNFa receptors (sTNF-R) and IL-10. In the present study we investigated the kinetics and the activation threshold for production of these mediators in E. coli lipopolysaccharide (LPS) or phytohaemagglutinin (PHA) stimulated whole blood cultures of 13 patients with systemic juvenile rheumatoid arthritis (SJRA) and 10 healthy children.

Results:

In unstimulated cultures the levels of IL-1b, IL-6 and TNFa were undetectable in both patients and controls suggesting that there was no spontaneous production of these cytokines by circulating leukocytes in SJRA. The activation thresholds for production of the cytokines were not decreased and the capacity for production the cytokines did not differ significantly from that of controls.

The IL-1ra level in plasma of the patients was significantly elevated (median 684 pg/ml versus 61 pg/ml, p =0.042). The in vitro production of IL-1ra was normal or sligtly elevated, depending upon stimulation procedure and incubation time, and it did not correlate with plasma levels of IL-1ra. Supernatant levels of sTNF-RI and II were both significantly elevated and correlated highly with the global activity score (sTNFR-I: r = 0.772, p < 0.02; sTNFR-II: r = 0.925, p < 0.002). In contrast the supernatant levels of IL-10 were reduced in both PHA and LPS driven cultures after 24-48h of incubation. Even though IL-10 levels did not correlate with laboratory or clinical indices of disease activity the results suggest that reduced IL-10 production may play a pathogenetic role in SJRA.