OBJECTIVE: Several clinical studies performed with human recombinant interleukin 10 (IL-10) in patients with rheumatoid arthritis (RA) have shown little efficacy. We investigated potentially proinflammatory in vivo effects of IL-10 in humans. We evaluated the upregulation of Fc gamma receptor (Fc gamma R) expression on monocytes/macrophages (and granulocytes) in patients with RA receiving different dosages of IL-10. METHODS: Together with changes in disease activity and several cell markers, the expression of Fc gamma RI, Fc gamma RIIa, and Fc gamma RIII was determined on granulocytes and monocytes/macrophages from the peripheral blood of 6 patients with active RA before and after treatment with recombinant human IL-10. In addition, the in vitro effect of IL-10 on Fc gamma R expression on monocytes/macrophages in combination with their susceptibility to immune complex induced production of tumor necrosis factor-alpha(TNF-alpha) was assessed. RESULTS: Clinical improvement was not observed in the IL-10 treated patients (based on ACR20 criteria). Significant decreases in thrombocyte numbers were observed in patients receiving IL-10. No changes in cell markers such as CD14 were found. On the other hand, expression of Fc gamma RI and Fc gamma RIIa on monocytes/macrophages was increased upon high dose IL-10 treatment. Interestingly, increases in expression of Fc gamma RI and Fc gamma RIIa correlated with a decrease in thrombocyte numbers. In vitro, IL-10 similarly upregulated Fc gamma RI and Fc gamma RIIa expression on monocytes/macrophages from RA patients. This was accompanied by increased TNF-a production after immune complex stimulation. CONCLUSION: These findings indicate that upregulation of Fc gamma R expression in RA with IL-10 treatment may counteract the otherwise antiinflammatory effects of IL-10 by potentiating immune complex mediated proinflammatory responses.
OBJECTIVE: Several clinical studies performed with human recombinant interleukin 10 (IL-10) in patients with rheumatoid arthritis (RA) have shown little efficacy. We investigated potentially proinflammatory in vivo effects of IL-10 in humans. We evaluated the upregulation of Fc gamma receptor (Fc gamma R) expression on monocytes/macrophages (and granulocytes) in patients with RA receiving different dosages of IL-10. METHODS: Together with changes in disease activity and several cell markers, the expression of Fc gamma RI, Fc gamma RIIa, and Fc gamma RIII was determined on granulocytes and monocytes/macrophages from the peripheral blood of 6 patients with active RA before and after treatment with recombinant humanIL-10. In addition, the in vitro effect of IL-10 on Fc gamma R expression on monocytes/macrophages in combination with their susceptibility to immune complex induced production of tumor necrosis factor-alpha(TNF-alpha) was assessed. RESULTS: Clinical improvement was not observed in the IL-10 treated patients (based on ACR20 criteria). Significant decreases in thrombocyte numbers were observed in patients receiving IL-10. No changes in cell markers such as CD14 were found. On the other hand, expression of Fc gamma RI and Fc gamma RIIa on monocytes/macrophages was increased upon high dose IL-10 treatment. Interestingly, increases in expression of Fc gamma RI and Fc gamma RIIa correlated with a decrease in thrombocyte numbers. In vitro, IL-10 similarly upregulated Fc gamma RI and Fc gamma RIIa expression on monocytes/macrophages from RApatients. This was accompanied by increased TNF-a production after immune complex stimulation. CONCLUSION: These findings indicate that upregulation of Fc gamma R expression in RA with IL-10 treatment may counteract the otherwise antiinflammatory effects of IL-10 by potentiating immune complex mediated proinflammatory responses.
Authors: Jonathan P Butchar; Payal Mehta; Steven E Justiniano; Kristan D Guenterberg; Sri-Vidya Kondadasula; Xiaokui Mo; Mahesh Chemudupati; Thirumala-Devi Kanneganti; Amal Amer; Natarajan Muthusamy; David Jarjoura; Clay B Marsh; William E Carson; John C Byrd; Susheela Tridandapani Journal: Clin Cancer Res Date: 2010-03-23 Impact factor: 12.531
Authors: Kavin Fatehchand; Li Ren; Saranya Elavazhagan; Huiqing Fang; Xiaokui Mo; John P Vasilakos; Gregory N Dietsch; Robert M Hershberg; Susheela Tridandapani; Jonathan P Butchar Journal: J Biol Chem Date: 2015-12-22 Impact factor: 5.157
Authors: Giulio Cavalli; Marije Koenders; Vassili Kalabokis; Jihye Kim; Aik Choon Tan; Cecilia Garlanda; Alberto Mantovani; Lorenzo Dagna; Leo A B Joosten; Charles A Dinarello Journal: Rheumatology (Oxford) Date: 2016-08-26 Impact factor: 7.580