Immune profiling of human vestibular schwannoma secretions identifies TNF-α and TWEAK as cytokines with synergistic potential to impair hearing

Table 1 Synergy parameters of TWEAK and TNF-α applied at constant and variable concentration ratios

Ratio	TWEAK + TNF-α (ng/mL)	Fractional inhibition (Fa)	CI	Description	DRI (TWEAK)	DRI (TNF-α)
Constant	0.05 + 0.05	0.01	11,026	Very strong antagonism	0.066	9.08E-05
	0.1 + 0.1	0.025	508.851	Very strong antagonism	0.7142	0.002
	1 + 1	0.092	22.311	Very strong antagonism	5.961	0.045
	10 + 10	0.509	0.022	Very strong synergism	1126.61	47.77
	50 + 50	0.95	1.30E-06	Very strong synergism	2.86E + 06	1.05E + 06
	100 + 100	0.99	1.65E-06	Very strong synergism	1.20E + 08	1.21E + 08
Variable	50 + 0.01	0.264	0.139	Strong synergism	7.25	701.11
	50 + 0.05	0.323	0.055	Very strong synergism	18.28	2,184.27
	50 + 0.1	0.491	0.006	Very strong synergism	177.94	35,762.60
	50 + 1	0.57	0.002	Very strong synergism	496.28	126,574
	50 + 10	0.906	3.74E-06	Very strong synergism	264,407	2.98E + 08
	50 + 50	0.95	6.99E-07	Very strong synergism	1.43E + 06	2.63E + 09
	50 + 100	0.97	2.04E-07	Very strong synergism	4.89E + 06	1.30E + 10

TWEAK and TNF-α were applied together at the constant (iso concentrations) and variable ratios (different concentrations of TNF-α). The Combination Index (CI) and Dose-Reduction Index (DRI) were calculated using the Chou-Talalay method through the CompuSyn software. According to the CI values, synergy is indicated by CI < 1, an additive effect by CI = 1, and antagonism by CI > 1. The DRI values represent the potential for dose reduction, where DRI > 1 suggests favorable dose reduction, DRI = 1 indicates no dose reduction, and DRI < 1 reflects an unfavorable dose reduction. ‘Fa’ denotes the fraction affected, representing the fractional inhibition of metabolic activity

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