ABSTRACT
Group 3 innate lymphoid cells (ILC3), which express IL-22 and IL-17A, has been introduced as one of pathologic cells in axial spondyloarthritis (axSpA). Dyslipidaemia should be managed in axSpA patients to reduce cardiovascular disease, and dyslipidaemia promotes inflammation. This study aimed to reveal the role of circulating ILC3 in axSpA and the impact of dyslipidaemia on axSpA pathogenesis. AxSpA patients with or without dyslipidaemia and healthy control were recruited. Peripheral blood samples were collected, and flow cytometry analysis of circulating ILC3 and CD4+ T cells was performed. The correlation between Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (CRP) and circulating immune cells was evaluated. The effect of oxidized low-density lipoprotein cholesterol (oxLDL-C) on immune cell differentiation was confirmed. AxSpA human monocytes were cultured with with oxLDL-C, IL-22, or oxLDL-C plus IL-22 to evaluate osteoclastogenesis using tartrate-resistant acid phosphatase (TRAP) staining and realtime quantitative PCR of osteoclast-related gene expression. Total of 34 axSpA patients (13 with dyslipidaemia and 21 without) were included in the analysis. Circulating IL-22+ ILC3 and Th17 were significantly elevated in axSpA patients with dyslipidaemia (p=0.001 and p=0.034, respectively), and circulating IL-22+ ILC3 significantly correlated with ASDAS-CRP (Rho=0.4198 and p=0.0367). Stimulation with oxLDL-C significantly increased IL-22+ ILC3, NKp44 − ILC3, and Th17 cells, and these were reversed by CD36 blocking agent. IL-22 and oxLDL-C increased TRAP + cells and osteoclast-related gene expression. This study suggested potential role of circulating IL-22+ ILC3 as biomarker in axSpA. Furthermore, dyslipidaemia augmented IL-22+ ILC3 differentiation, and oxLDL-C and IL-22 markedly increased osteoclastogenesis of axSpA.
ABSTRACT
BACKGROUND: We investigated how one pharmacokinetic (PK) model differed in prediction of plasma (Cp) and effect-site concentration (Ceff) using a reproducing simulation of target-controlled infusion (TCI) with another PK model of propofol. METHODS: Sixty female patients were randomly assigned to TCI using Marsh PK (Group M) and TCI using Schnider PK (Group S) targeting 6.0 microg/ml of Cp of propofol for induction of anesthesia, and loss of responsiveness (LOR) was evaluated. Total and separate cross-simulation were investigated using the 2 hr TCI data (Marsh TCI and Schnider TCI), and we investigated the reproduced predicted concentrations (MARSHSCH and SCHNIDERMAR) using the other model. The correlation of the difference with covariates, and the influence of the PK parameters on the difference of prediction were investigated. RESULTS: Group M had a shorter time to LOR compared to Group S (P < 0.001), but Ceff at LOR was not different between groups. Reproduced simulations showed different time courses of Cp. MARSHSCH predicted a higher concentration during the early phase, whereas SCHNIDERMAR was maintained at a higher concentration. Volume and clearance of the central compartment were relevant to the difference of prediction, respectively. Body weight correlated well with differences in prediction between models (Rsqr = 0.9821, P < 0.001). CONCLUSIONS: We compared two PK models to determine the different infusion behaviors during TCI, which resulted from the different parameter sets for each PK model.