Fig 4. Suppression of monocyte-derived, pro-inflammatory cytokine secretion by TO-207 and IL-6/IL-1 pathway–specific suppression by tocilizumab/anakinra.

A) Effects on cytokine production by LPS- and ATP-stimulated monocytes. Peripheral blood mononuclear CD14⁺ cells (2 × 10⁵) were seeded in a 96-well plate with culture medium containing PSL or TO-207. The cells were stimulated with 100 ng/mL LPS for 3 h, and then with 5 mM ATP for 2 h. Supernatants were recovered, and cytokine levels were determined. The error bars represent SEs from three independent experiments. B) Wide-ranging suppression of monocyte-derived pro-inflammatory cytokines by TO-207. K562/CD19 cells (3 × 10³), CAR T cells (1.5 × 10⁴), and CD14⁺ cells (1.5 × 10⁴) were co-cultured in a 96-well plate in the absence or presence of PSL or TO-207. After 72 h of co-culture, the supernatants were recovered, and cytokine levels were determined. The error bars represent SEs from three independent experiments. The linear dose-response relationship was assessed using log-transformed dose values (to the base 10) in a mixed model, in which the zero dose was replaced by the log (minimal dose) - 1. P < 0.05 was considered statistically significant. n.s.: not significant. n.d.: not detected.