Increased peripheral T cell reactivity to microbial antigens and collagen type II in rheumatoid arthritis after treatment with soluble TNF alpha receptors

Objective-Peripheral T cells from patients with rheumatoid arthritis (RA) a re hyporesponsive when stimulated with antigen or mitogen in vitro, possibl y owing to increased production of proinflammatory cytokines such as tumour necrosis factor alpha (TNF alpha). This study sought to find out if and ho w RA T eel reactivity is affected during treatment with etanercept (Enbrel) , a soluble TNF alpha receptor, Methods-Heparinised blood was collected from patients with RA at baseline, after four and eight weeks of etanercept treatment, and from healthy contro ls. After density separation spontaneous production of interferon gamma (IF N gamma), TNF alpha, interleukin 6 (IL6), and IL10 by peripheral blood mono nuclear cells (PBMC) was detected by ELISPOT. For detection of T cell react ivity, PBMC were stimulated in vitro with mitogen (phytohaemagglutinin (PHA )), microbial antigens (purified protein derivative (PPD), influenza), or a n autoantigen, collagen type II (CII). Supernatants were analysed for IFN g amma and IL2 content by enzyme linked immunosorbent assay (ELISA). Results-In RA the number of cells spontaneously producing IFN gamma was sig nificantly increased after four, but not eight weeks' treatment with etaner cept. T cell reactivity, as measured by IFN gamma production to PPD, influe nza, and CII was significantly increased after four and sustained after eig ht weeks' treatment, whereas IFN I production induced by PHA remained uncha nged. TNF alpha production was significantly higher in patients with RA tha n in controls and did not change during etanercept treatment. Conclusion-Treatment of patients with RA with etanercept may lead to increa sed peripheral T cell reactivity both to microbial antigens and to self ant igens such as CII. These findings indicate that TNF alpha blockade may not only suppress but also stimulate certain aspects of antimicrobial immune de fence and autoimmunity.