Dual effects of interleukin-10 on natural killer cells and monocytes and the implications for adult-onset Still's disease

Objective. 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-)gamma. IL-6 had little effect on NK cells, probably because they barely expressed the IL-6 receptor and glycoprotein 130 (gp130). IFN-gamma induced monocytes to produce IL-1 beta, IL-6 and tumour necrosis factor (TNF-)alpha whereas IL-10 inhibited the induction of these proinflammatory cytokines. Conclusion. 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.

Automated summary

The study found that IL-6 and IL-18 were the main cytokines increased in the serum of AOSD patients. When NK cells were cultured with IL-10 and IL-18, it significantly induced the production of IFN-gamma, while IL-10 inhibited the production of proinflammatory cytokines by monocytes. These findings suggest that IL-10 has dual effects on NK cells and monocytes in AOSD patients.