Yoshimi Aizaki1, Hiroaki Yazawa2, Kojiro Sato3, Toshihide Mimura1. 1. Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Saitama, Japan. 2. Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Saitama, and Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University, Tochigi, Japan. 3. Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University, Tochigi, Japan. satok@jichi.ac.jp.
Abstract
OBJECTIVES: We compared the serum levels of multiple cytokines in patients with adult-onset Still's disease (AOSD) and healthy controls to assess the effects of humoral factors on natural killer (NK) cells and monocytes. METHODS: We quantified the serum levels of 10 cytokines in the patients using bead-based multiplex immunoassays, along with interleukin (IL-)18 using ELISA. We then sorted NK cells and monocytes from the peripheral blood mononuclear cells (PBMCs) of healthy volunteers, cultured them in the presence or absence of cytokines that were detected in some or all of the serum samples from the AOSD patients and their combinations in vitro, and analysed the culture supernatant. RESULTS: IL-6 and IL-18 were the main cytokines increased in the serum of AOSD patients. When NK cells were cultured with the cytokines and IL-10, the combination of IL-10 and IL-18 substantially induced interferon (IFN-)γ. IL-6 had little effect on NK cells, probably because they barely expressed the IL-6 receptor and glycoprotein 130 (gp130). IFN-γ induced monocytes to produce IL-1β, IL-6 and tumour necrosis factor (TNF-)α whereas IL-10 inhibited the induction of these proinflammatory cytokines. CONCLUSIONS: IL-10 evidently has dual effects on NK cells (stimulation) and on monocytes (inhibition). Better understanding the roles of the cytokine network would shed light on the pathogenesis of AOSD.
OBJECTIVES: We compared the serum levels of multiple cytokines in patients with adult-onset Still's disease (AOSD) and healthy controls to assess the effects of humoral factors on natural killer (NK) cells and monocytes. METHODS: We quantified the serum levels of 10 cytokines in the patients using bead-based multiplex immunoassays, along with interleukin (IL-)18 using ELISA. We then sorted NK cells and monocytes from the peripheral blood mononuclear cells (PBMCs) of healthy volunteers, cultured them in the presence or absence of cytokines that were detected in some or all of the serum samples from the AOSD patients and their combinations in vitro, and analysed the culture supernatant. RESULTS: IL-6 and IL-18 were the main cytokines increased in the serum of AOSD patients. When NK cells were cultured with the cytokines and IL-10, the combination of IL-10 and IL-18 substantially induced interferon (IFN-)γ. IL-6 had little effect on NK cells, probably because they barely expressed the IL-6 receptor and glycoprotein 130 (gp130). IFN-γ induced monocytes to produce IL-1β, IL-6 and tumour necrosis factor (TNF-)α whereas IL-10 inhibited the induction of these proinflammatory cytokines. CONCLUSIONS: IL-10 evidently has dual effects on NK cells (stimulation) and on monocytes (inhibition). Better understanding the roles of the cytokine network would shed light on the pathogenesis of AOSD.