Fig. 1.

Inter-individual differences in stimulated cytokine responses in patients with mitochondrial disease. a Schematic of study groups included in whole blood LPS experiments. b Pro-inflammatory cytokine (IL-6, TNF-α, and IL-1β) levels from healthy controls, patients with 3243A > G mutation and single deletions after 6 h of exposure to increasing concentrations of LPS. The grey boxes indicate missing/undetermined data. c Dose-dependent cytokine responses and fitted models used to determine the maximal (ECmax) and half maximal concentration of LPS (EC₅₀) in controls (grey) and in patients with mitochondrial disease (green = mutation, orange = deletion). d Inter-individual differences in cytokine sensitivity among patients with mitochondrial diseases and healthy controls. e Cytokine sensitivity bi-plots based on LPS EC₅₀ values. The dotted line crosses the origin and average of the control group. f Standardized effect sizes (Hedge’s g) of cytokine response (EC₅₀, left; max response, right) in mitochondrial disease groups relative to healthy controls. g > 0.5 is a medium effect size, and g > 0.8 is a large effect size. Non-linear regression analysis was used in dose–response curves presented in c, and one-way ANOVA with Dunnett’s multiple comparison post hoc analysis was used in d. *p < 0.05; **p < 0.01; ns not significant. Assays were performed once in technical duplicates. Error bars indicate SEM in all panels. Controls n = 21, Mutation n = 7, Deletion n = 5