Effects of AG490 on production of interleukin-2, 6 and interferon-gamma in human lymphocyte proliferation: Is the effect equal to Cyclosporine A or FK506? / 中国组织工程研究

ABSTRACT

BACKGROUND: AG490 is a newly found JAK kinase inhibitor, which can compete with receptor tyrosine kinase for binding site to block JAK/STAT pathway, inhibit rejection-related cytokine activation such as interferon-gamma (IFN-γ) ultimately inhibiting rejection.OBJECTIVE: To evaluate the possibility and prospect of the AG490 as a potential immunosuppressor, explore its basic mechanism in comparison with Cyclosporine A (CsA).DESIGN, TIME AND SETTING: Comparative observation was performed at the Institute of Urinary Surgery, Fujian Union Hospital from October 2007 to April 2008.MATERIALS AG490 was purchased from Sigma, USA.METHODS: Human peripheral blood lymphocyte (both T and B) were harvested from 8 healthy donors. Lymphocyte were isolated by density gradient method and cultured with phytohemagglutinin, interleukin-2 (IL-2) or mixed lymphocyte culture to induce human lymphocyte proliferation. MAIN OUTCOME MEASURES: ELISA was used to detect the concentration of IL-2, IFN-γ and IL-6 in different culture systems with the tyrphostin (AG490), CsA or FK506. RESULTS: IL-2 and IFN-γ in culture systems of phytohemagglutinin, IL-2 or mixed lymphocyte culture were inhibited by AG490 (P < 0.05), but IL-6 was not suppressed by AG490 (P < 0.05). This effect was similar to clinical CsA or FK506. CONCLUSION: AG490 may be a potential immunosuppressor.