Abstract: Effect of treatment of rheumatoid arthritis with infliximab on IFNg, IL-4, T-bet, and GATA-3 expression: link with improvement of systemic inflammation and disease activity

Ann Rheum Dis. 2004 Jul 29 [Epub ahead of print] Kawashima M, Miossec P. Clinical Immunology Lyon, France.

OBJECTIVES: Reduced IFNg production in response to Th1 inducing cytokines such as IL-12 or IL-18 has been described in PBMC from RA patients. To distinguish between a disease specific- or disease activity- dependent defect, RA PBMC before and during infliximab treatment were studied for IFNg production and the expression of profiles of T-bet and GATA-3, the transcription factors associated with Th1 and Th2.

METHODS: RA PBMC were obtained at week 0 and 6 of infliximab treatment and cultured 7 days with or without IL-12 and the combination of IL-12 and IL-18. IFNg levels in supernatants were determined by ELISA. mRNA expression of IFNg, IL-4, T-bet, and GATA-3 was determined by real-time RT-PCR in whole blood at week 0 and 22.

RESULTS: A reduction of the spontaneous IFNg production and of the response to Th1 inducing cytokines was observed in RA PBMC. Reduction of the systemic inflammation with infliximab treatment increased IFNg production in response to IL-12 or IL-12+IL-18. IFNg/IL- 4 expression ratio of RA blood before treatment was lower than that of healthy controls (HC), but it was significantly increased by infliximab treatment. T-bet expression or T-bet/GATA-3 ratio of RA blood was lower than that of HC. The T-bet/GATA-3 ratio was not influenced by infliximab treatment.

CONCLUSIONS: Regulation of T-bet and GATA-3 or IFNg and IL-4 expression appeared to be different. The IFNg/IL-4 ratio might express better the blood Th1/Th2 balance than the T-bet/GATA-3 ratio. Reduced IFNg production by RA PBMC and levels of IFNg and IL-4 mRNA expression in blood were linked to disease improvement, indicating the association between this systemic Th1 feature and disease activity.

PMID: 15286007 [PubMed – as supplied by publisher]

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