TABLE 5.

List of target-related parameters used for anti-IL-33 model.

Parameter	Description	Value, units	Comments and references
IL33s_0	Initial concentration of free IL-33 at the SoA (lung)	11 pM	200 pg/mg of lung tissue in COPD or asthmatic patients (Cohen et al., 2015)
IL33p_0	Initial concentration of free IL-33 in plasma	1.5 pM	Assumed similar between asthma and allergic rhinitis – 27 pg/ml (Glück et al., 2019)
sST2_0	Initial concentration of free sST2 in plasma	27 pM	1 ng/ml in mild/moderate attack ((Oshikawa et al., 2001)), within two-fold of most other situations in Oshikawa et al. (2001) and levels in Glück et al. (2019)
sST2_IL33p_0	Initial concentration of sST2-bound IL-33 in plasma	$={\text{ k}}_{on\_ST2}\text{∗ IL}33{\text{p}}_0\text{∗}\frac{\text{sST}2{\text{p}}_0}{{\text{k}}_{off\_ST2}+{\text{ k}}_{\text{deg}\_\text{sST}2\_\text{IL}33\text{p}}}$	To preserve drug-free equilibrium values
IL-33 molecular weight	To convert mass concentration into molarity	18 kDa	Palmer et al. (2008)
sST2 molecular weight	To convert mass concentration into molarity	37 kDa	Mueller and Dieplinger, (2016)
kdeg_IL33p	Degradation rate of IL-33 in plasma	4.2 1/day	∼4 h half-life in human lung explants (Cohen et al., 2015)
kdeg_sST2p	Degradation rate of sST2 in plasma	2.6 1/day	6.3 h half-life (recombinant, IV administration) (Jacobs et al., 1993)
kdeg_sST2_IL33p	Degradation rate of sST2:IL-33 complex in plasma	$={\text{ k}}_{\text{deg}\_\text{sST}2\text{p}}$	Assumed
kon_ST2	Association constant between IL-33 and sST2	358 1/nM/day	Palmer et al. (2008)
koff_ST2	Dissociation rate between IL-33 and sST2	$={\text{ k}}_{\text{on}\_\text{ST}2}{\text{∗ K}}_{\text{D}\_\text{IL}33\_\text{sST}2}$	KD_IL33_sST2 = 26 pM (Palmer et al., 2008)
kps_IL33	IL-33 distribution rate from plasma to SoA	0.13 1/day	See Estimating Target Distribution
ksp_IL33	IL-33 distribution rate from SoA to plasma	$=\left({\text{k}}_{\text{ps}\_\text{IL}33\text{p}}\text{∗ IL}33{\text{p}}_0\right)\text{∗}\frac{{\text{V}}_P}{{\text{V}}_{\text{S}}\text{*IL}33{\text{s}}_0}+\frac{{\text{k}}_{\text{syn}\_\text{IL}33\text{s}}}{\text{IL}33{\text{s}}_0}$	To preserve drug-free equilibrium values
ksyn_IL33s	IL-33 synthesis rate at the SoA	$=\left({\text{k}}_{\text{deg}\_\text{IL}33\text{p}}\text{∗ IL}33{\text{p}}_0+{\text{ k}}_{\text{deg}\_\text{sST}2\_\text{IL}33\text{p}}\text{∗ sST}2\_\text{IL}33{\text{p}}_0\right)\text{∗}\frac{{\text{V}}_{\text{P}}}{{\text{V}}_{\text{S}}}$	To preserve drug-free equilibrium values
ksyn_sST2p	sST2 synthesis rate in plasma	$={\text{ k}}_{\text{deg}\_\text{sST}2\text{p}}\text{∗ sST}2{\text{p}}_0+{\text{k}}_{\text{deg}\_\text{sST}2\_\text{IL}33\text{p}}\text{∗ sST}2\_\text{IL}33{\text{p}}_0$	To preserve drug-free equilibrium values