Figure 5. IL-10 constitutes an additional mechanism mediating the protective capacities of NAD⁺ in the context of septic shock.

(A) Caspase-11 KO (knockout) mice were treated with NAD⁺ or PBS. Subsequently mice were subjected to poly(I:C) prior to lipopolysaccharide (LPS) injection and survival was monitored (n=5, 2 independent survival experiments). Mice treated with either NAD⁺ or PBS were injected with LPS and after 10 hr, splenic frequencies of IL-10 producing (B) macrophges and dendritic cells (C) and CD4+ and CD8+ T cells were assessed by flow cytometry. Box plots display fold change of leukocyte proportions as mean with standard deviation (n=5) (D) Bone marrow-derived macrophages (BMDMs) treated with NAD⁺ or PBS were stimulated with LPS and cholera toxin B (CTB) in the presence of IL-10 neutralizing antibodies and IL-10 receptor antagonists. Subsequently IL-1β and LDH release were assessed. Column plots display mean with standard deviation (n=6) (E) IL-10-/- mice treated with NAD⁺ or PBS were challenged with LPS and survival was monitored (n=5–7, 2 independent survival experiments). Statistical significance was determined by using Student’s t-test or one-way ANOVA while survival data were compared using log-rank Mantel-Cox test. Asterisks indicate p-values *=p<0.05, **=p<0.01, and ***=p<0.001, only significant values are shown. All data depicted in this figure are provided as source data.