C-reactive protein (CRP) response is abnormal to a non-infectious inflammation in systemic lupus erythematosus (SLE). We evaluated the role of cytokines in this CRP unresponsiveness. The sera of 138 SLE patients and 71 rheumatoid arthritis patients were collected prospectively. SLE with infection had higher WBC count, ESR, CRP and C4 levels than those without infection. IL-6, IL-10 and IFN-gamma levels were higher in SLE with infection than SLE without infection. In SLE with infection, the CRP was correlated with the IL-6 (r = 0.77, P < 0.001) but not correlated with IL-10 and IFN-gamma. These data suggest that IL-6 may have a role in the unresponsiveness of CRP to a non-infectious inflammation of SLE.