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Effect of treatment of rheumatoid arthritis with infliximab on IFN, IL4, T-bet, and GATA-3 expression: link with improvement of systemic inflammation and disease activity

M Kawashima, P Miossec

Department of Immunology and Rheumatology and INSERM U-403, Hospital Edouard Herriot, Lyon, France

Correspondence to:
Professor P Miossec
Clinical Immunology Unit, Department of Immunology and Rheumatology, Hospital Edouard Herriot, 69437 Lyon Cedex 03, France; miossec{at}univ-lyon1.fr

Objective: To study interferon (IFN) production and the expression of T-bet and GATA-3, the transcription factors associated with Th1 and Th2, in peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis before and during infliximab treatment, so as to distinguish between a disease specific and a disease activity dependent defect.

Methods: Rheumatoid PBMC were obtained at weeks 0 and 6 of infliximab treatment and cultured for seven days with or without interleukin (IL)12 or the combination of IL12 and IL18. IFN concentrations in supernatants were determined by ELISA. mRNA expression of IFN, IL4, T-bet, and GATA-3 was determined by real time RT-PCR in whole blood at weeks 0 and 22.

Results: A reduction in spontaneous IFN production and in the response to Th1 inducing cytokines occurred in rheumatoid PBMC. Reduction of systemic inflammation with infliximab treatment increased IFN production in response to IL12 or IL12+IL18. The IFN/IL4 expression ratio of rheumatoid blood before treatment was lower than in healthy controls but was increased by infliximab treatment. T-bet expression or T-bet/GATA-3 ratio of rheumatoid blood was less than in controls. The T-bet/GATA-3 ratio was not influenced by infliximab treatment.

Conclusions: Regulation of T-bet and GATA-3 or IFN and IL4 expression appeared different. The IFN/IL4 ratio might express the blood Th1/Th2 balance better than the T-bet/GATA-3 ratio. Reduced IFN production by rheumatoid PBMC and levels of IFN and IL4 mRNA expression in blood were linked to disease improvement, indicating an association between this systemic Th1 feature and disease activity.

Abbreviations: ACR, American College of Rheumatology; IFN, interferon ; IL, interleukin; PBMC, peripheral blood mononuclear cells; Th, T helper cell; TNF, tumour necrosis factor

Keywords: rheumatoid arthritis; peripheral blood; infliximab; Th1/Th2 balance

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