[Why C-reactive protein is (usually) not high in SLE]

High levels of C‑reactive protein (CRP) in systemic lupus erythematosus are not usually a sign of disease activity but more of a severe bacterial infection. Why this is the case, even though levels of interleukin‑6 (IL-6) the most important CRP stimulator, are high in active SLE, has long been an intriguing question. Newly published results now provide an answer: in combination with interferon-alpha (IFNα), IL‑6 causes the IL‑6 receptor to be shed, i.e. enzymatically cleaved from the cell membrane. The soluble receptors constitute an IL‑6 buffer that inhibit IL‑6 biological activity in plasma. As this prevents IL‑6 from stimulating liver cells, no CRP is induced there. When IL‑6 levels are extremely high in the context of infections (and rarely lupus serositis or arthritis), the buffering capacity is exceeded and the hepatocytes respond by producing CRP.