Pathogenic Role of IL-6 Combined with TNF-a or IL-1 in the Induction of Acute Phase Proteins SAA and CRP in Chronic Inflammatory Diseases

摘要

The fact that acute phase proteins, such as C-reactive protein (CRP) and serum amyloid A (SAA), are elevated during inflammation is known to nearly all medical practitioners. However, exact mechanism for induction of these acute phase proteins, both in vitro and in vivo, remains unknown. IL-6 induces inflammatory status in autoimmune diseases. Consequently, IL-6 blocking therapy with an anti-IL-6 receptor antibody (tocilizumab) for Castleman's disease (CD) [1, 2], rheumatoid arthritis (RA) [3], and juvenile idiopathic arthritis (JIA) [4] led to improvement in most clinical symptoms and laboratory findings. CRP and SAA levels in particular were reduced and completely normalized, even if another cytokines and chemokines were activated in patients with RA. On the other hand, single use of TNF-alpha blockers, such as infliximab or etanercept, reduced SAA and CRP levels in RA patients, but barely to within normal range [5]. In this study, to clarify the different pathologic roles of IL-6 and TNF-alpha or IL-1 in induction of SAA and CRP in chronic inflammatory disease, we used hepatoma-derived cell lines to analyze the difference between the IL-6 and TNF-a mechanism in vitro, and between IL-6 and TNF-a blocking therapy for RA in vivo.