Interleukin 1 (IL-1) receptor antagonist, soluble tumor necrosis factor receptors, IL-1 beta, and IL-8--markers of remission in rheumatoid arthritis during treatment with methotrexate.

OBJECTIVE

To examine circulating levels of cytokines and cytokine inhibitors and their production by blood mononuclear cells (MNC) in patients with active rheumatoid arthritis (RA) before treatment with methotrexate (MTX) and inactive disease upon treatment as well as healthy control individuals.

METHODS

Interleukin-1 receptor antagonist (IL-1ra), soluble tumor necrosis factor receptors p55 and p75 (sTNFr; p55 and p75), interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8), and monocyte chemoattractant protein 1 (MCP-1) were assessed by immunoassays in sera and MNC culture supernatants of 27 patients with RA with active disease before and 14 patients with inactive disease during MTX treatment, and 10 healthy controls.

RESULTS

Levels of circulating IL-1ra, sTNFr p55 and p75 were higher in patients with active RA compared to those with inactive disease or controls. At the cellular level, resting MNC of patients with active RA released more IL-1 beta and IL-8, but less IL-1ra, and showed a lower ratio of IL-1ra:IL-1 beta than MNC of patients without inflammatory symptoms or healthy controls. In addition, unstimulated and in vitro lipopolysaccharide stimulated MNC cultures of patients with inactive RA released higher amounts of sTNFr p75 than MNC of patients with active RA.

CONCLUSION

Circulating levels of IL-1ra and sTNFr as well as IL-1 beta, IL-8, and sTNFr p75 release from MNC and the ratio of IL-1ra:IL-1 beta production by these cells serve as markers to assess complete disease remission in patients with RA during MTX treatment.