Elevated serum interleukin-6 levels associated with active disease in systemic connective tissue disorders

Abstract

Objective: It is well established that connective tissue diseases such as systemic lupus erythematosus (SLE) are associated with a weak or absent acute phase response, although elevated serum interleukin 6 levels have been described. In this study, we have sought to correlate serum levels of IL-6 with standard laboratory and clinical assessments of disease activity in two connective tissue diseases, namely SLE and systemic sclerosis (SSc), and, for comparative purposes, rheumatoid arthritis (RA).

Methods: Serum IL-6 levels were determined by bioassay and also, in some sera, by immunoradiometric assay. They were compared with two inflammatory parameters, serum C-reactive protein (CRP) and plasma viscosity (PV), and with appropriate clinical measurements in the various patient groups, including BILAG in SLE, the skin score in SSc, and the Ritchie index in RA.

Results: Serum IL-6 (SeIL-6) levels were elevated in active SLE, SSc, and RA. This was poorly correlated with the acute phase response in SLE and SSc, but there was a strong relationship of SeIL-6 to disease activity in these conditions. In SLE, the BILAG disease activity index correlated best with SeIL-6 levels while there was only a weak relationship between CRP and IL-6, and no relationship between CRP and disease activity. In SSc there was a relationship of disease activity to SeIL-6 but not between SeIL-6 and either CRP or PV. In a small RA group there was a much stronger relationship of SeIL-6 to CRP and PV, as has been previously described.

Conclusion: The determination of SeIL-6 may be a useful indicator of disease activity in those patients groups, including SLE and SSc, in which a normal acute phase response by the liver is often lacking. The mechanism underlying this hepatic impairment requires further investigation, but is clearly not due to a failure to generate the appropriate cytokine signal. Excessive local or systemic production of IL-6 in connective tissue diseases could play an important pathogenic role in these conditions, for example through stimulating autoantibody synthesis.