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BIOMD0000000536 - Dwivedi2014 - Crohns IL6 Disease model - sgp130 activity

 

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Reference Publication
Publication ID: 24402116
Dwivedi G, Fitz L, Hegen M, Martin SW, Harrold J, Heatherington A, Li C.
A multiscale model of interleukin-6-mediated immune regulation in Crohn's disease and its application in drug discovery and development.
CPT Pharmacometrics Syst Pharmacol 2014; 3: e89
The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.  [more]
Model
Original Model: BIOMD0000000536.origin
Submitter: Vincent Knight-Schrijver
Submission ID: MODEL1408050003
Submission Date: 05 Aug 2014 13:55:21 UTC
Last Modification Date: 11 Sep 2014 16:46:26 UTC
Creation Date: 06 Aug 2014 11:45:44 UTC
Encoders:  Vincent Knight-Schrijver
set #1
bqbiol:hasTaxon Taxonomy Homo sapiens
set #2
bqbiol:hasPart Gene Ontology JAK-STAT cascade
set #3
bqbiol:isVersionOf Gene Ontology interleukin-6 receptor activity
set #4
bqbiol:hasVersion Human Disease Ontology Crohn's disease
set #5
bqbiol:isPartOf Reactome REACT_27307.1
Notes
Dwivedi2014 - Crohns IL6 Disease model - sgp130 activity
This model is comprised of four models:
Possible avenues for Interleukin-6 (IL-6) inhibition in treating Crohn's disease are compared here. Each model refers to separate ligands. The system simulates differential activity of the ligands on the signalling of IL-6. This affects Signal Transducer and Activator of Transcription 3 (STAT3) activity on the production of biomarker C-Reactive Protein (CRP) expression.
The figure referring to this Crohn's Disease model is 6b.

This model is described in the article:

Dwivedi G, Fitz L, Hegen M, Martin SW, Harrold J, Heatherington A, Li C.
CPT Pharmacometrics Syst Pharmacol 2014; 3: e89

Abstract:

In this study, we have developed a multiscale systems model of interleukin (IL)-6-mediated immune regulation in Crohn's disease, by integrating intracellular signaling with organ-level dynamics of pharmacological markers underlying the disease. This model was linked to a general pharmacokinetic model for therapeutic monoclonal antibodies and used to comparatively study various biotherapeutic strategies targeting IL-6-mediated signaling in Crohn's disease. Our work illustrates techniques to develop mechanistic models of disease biology to study drug-system interaction. Despite a sparse training data set, predictions of the model were qualitatively validated by clinical biomarker data from a pilot trial with tocilizumab. Model-based analysis suggests that strategies targeting IL-6, IL-6R?, or the IL-6/sIL-6R? complex are less effective at suppressing pharmacological markers of Crohn's than dual targeting the IL-6/sIL-6R? complex in addition to IL-6 or IL-6R?. The potential value of multiscale system pharmacology modeling in drug discovery and development is also discussed.CPT: Pharmacometrics & Systems Pharmacology (2014) 3, e89; doi:10.1038/psp.2013.64; advance online publication 8 January 2014.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Model
Publication ID: 24402116 Submission Date: 05 Aug 2014 13:55:21 UTC Last Modification Date: 11 Sep 2014 16:46:26 UTC Creation Date: 06 Aug 2014 11:45:44 UTC
Mathematical expressions
Reactions
reaction_1 reaction_2 reaction_3 reaction_4
reaction_5 reaction_6 reaction_7 reaction_8
reaction_16 reaction_9 reaction_10 reaction_15
reaction_11 reaction_12 reaction_13 reaction_14
reaction_41 reaction_46 reaction_42 reaction_43
reaction_44 reaction_45 mwb675e13a_26c0_4b18_a8c3_0f5a62090ba4 mw64df7c9e_35da_4c7f_be56_c5dabfb060b6
mw391f3b8e_5649_4851_b2e2_782cb3e015b6 mw4a00a3a4_778f_4952_8100_2dc3cc2b7046 mw6db30657_4e56_4c3a_8575_9c67393dde4f mw6f470e13_f0e4_4294_83d8_59dd5670d10c
mwfb35eca9_7afc_4ba8_a46c_738cab57eb9f mw61d2af92_6da5_41ce_b90e_aa6f430e6ba1 mw4c099d5c_200f_474e_8ec1_59e9223a8afd mwbe8567ce_3349_4442_8b12_53cd9bc168e7
mw12a9fa7e_a273_4c1e_b970_ed33f3a9a705 mw1046000b_e1e8_4f6f_82a1_532d2aa793bb mw8e8b65a8_6830_4091_9a40_19645e8fe554 mwa812f08f_1035_42bd_82d2_72d691308f88
mwab0012ac_e5f2_4904_9893_820fd210402e mwcdc24bd4_d9e4_47fe_8300_d222d853111c mwff2ebcf1_dcf1_47b9_9cac_7306fc6f7f76 mw1c5a5ff7_5130_490f_a740_6a744ccf8a94
mw7b56053c_7256_4703_a8c3_4fd46b2c23d0 mw8be158f1_ea81_45bf_80d4_6e31cd83fe6c mwd77df15b_fed7_41a8_a3d6_b0f6c590c5f6 mw01babcdf_0f03_46b0_81b1_201cc846e361
mwae5dbb44_7de5_46ab_8c20_ac4f8956b0f0 mw432fde6e_59ab_47f0_9fb1_086433a602e3 mw41c27823_d7ee_4554_9eac_3d5beec8e854 mw50c6744c_e883_4612_8663_e38750cbad1b
mwb6a99eb5_ea4c_4733_98dd_1daf5ec6b0db mw1ce0c484_681f_4d85_8ffe_392d0c100cfa mwf913ea0b_785a_4701_ac91_b18ab5dd5a89 mw71d90b81_8211_4039_8807_12a7fe03206c
mwdf4ba845_7271_4ada_b43f_fdac83df3b5c mwc32a28fa_525c_44af_8d2c_e728c21eb90a mw14d351b9_623a_48e8_a21c_854411039120 mwba7f4605_8571_439b_b3ab_eb0b43808db8
mw5be6711a_526a_4a58_80c6_d353dcabdf87 mw1d3068d7_5679_41ee_9892_984e33012070 mwb341c690_7147_46a1_8577_201598de3bf1 mw5d9fcd0c_ca08_4444_b509_2ea4777e0025
mw131e3c9d_e77d_48c0_bdbb_77b2c10aaf3d mw14940d1f_6a1f_47cb_8170_801ba645f4c1 mwb62106e7_e959_4a1d_9a00_b36d4e19a48f mwad648b6c_45ca_4f41_9747_06db1f6060fc
mw2ae288ab_7d03_4a84_a024_c711ad2b77e6 mw9629d028_fcc0_4886_9e4d_36eecdb0381d    
Rules
Assignment Rule (variable: CRP Suppression (%)) Assignment Rule (variable: geneProduct) Assignment Rule (variable: CRP)  
Events
Week1 Week2 Week3 Week4
Week5 Week6 Week7 Week8
Week9 Week10 Week11 Week12
Week0      
Physical entities
Compartments Species
serum IL6 sgp130 sR_IL6_sgp130
CRP sR sR_IL6
sgpFc sR_IL6_sgpFc CRP Suppression (%)
liver gp130 R_IL6_gp130 sR_IL6
R IL6 R_IL6
Ractive STAT3 pSTAT3
CRP sR CRPExtracellular
sgp130 sR_IL6_sgp130 sR_IL6_sgpFc
sgpFc    
gut sR_IL6 gp130 R_IL6_gp130
Ractive STAT3 pSTAT3
geneProduct sR IL6
sgp130 sR_IL6_sgp130 sgpFc
sR_IL6_sgpFc    
peripheral sgpFc    
Global parameters
kRLOn kRLOff kgp130On kgp130Off
kRAct kRint kRsynth kRintBasal
ksynthIL6 kdegIL6 kdegCRP KmSTATDephos
VmSTATDephos VmRDephos KmRDephos kcatSTATPhos
KmSTATPhos KmProtSynth VmProtSynth kCRPSecretion
ksynthCRP ksynthsR kdegsR ksynthsgp130
kdegsgp130 ksynthIL6Gut kdegIL6Gut kdistTissueToSerum
kdistSerumToTissue kRShedding kintActiveR infusionTime
kAbSerumToLiver kAbLiverToSerum kAbSerumToGut kAbGutToSerum
VSerum VLiver VGut VPeriph
QSerumLiver QSerumGut QSerumPeriph kAbSerumToPeriph
kAbPeriphToSerum kdegAb Dose Q1W Dose Q2W
Dose Q4W Initial for CRP Initial for Dose Q1W Initial for Dose Q2W
Initial for Dose Q4W      
Reactions (66)
 
 reaction_1 [sR] + [IL6] ↔ [sR_IL6];   {sR_IL6} , {sR} , {IL6}
 
 reaction_2 [sR_IL6] + [sgp130] ↔ [sR_IL6_sgp130];   {sR_IL6} , {sR_IL6_sgp130} , {sgp130}
 
 reaction_3  → [IL6];  
 
 reaction_4 [IL6] → ;   {IL6}
 
 reaction_5 [CRP] → ;   {CRP}
 
 reaction_6 [sR_IL6] + [gp130] ↔ [R_IL6_gp130];   {sR_IL6} , {gp130} , {R_IL6_gp130}
 
 reaction_7 [R] + [IL6] ↔ [R_IL6];   {IL6} , {R} , {R_IL6}
 
 reaction_8 [R_IL6] + [gp130] ↔ [R_IL6_gp130];   {R_IL6} , {gp130} , {R_IL6_gp130}
 
 reaction_16 [R_IL6_gp130] → [Ractive];   {R_IL6_gp130}
 
 reaction_9 [STAT3] + [Ractive] → [pSTAT3] + [Ractive];   {Ractive} , {STAT3}
 
 reaction_10 [pSTAT3] → [STAT3];   {pSTAT3}
 
 reaction_15 [R] → ;   {R}
 
 reaction_11 [R_IL6] → ;   {R_IL6}
 
 reaction_12 [R_IL6_gp130] → ;   {R_IL6_gp130}
 
 reaction_13 [Ractive] → ;   {Ractive}
 
 reaction_14  → [R];  
 
 reaction_41 [sR_IL6] + [gp130] ↔ [R_IL6_gp130];   {sR_IL6} , {R_IL6_gp130} , {gp130}
 
 reaction_46 [R_IL6_gp130] → [Ractive];   {R_IL6_gp130}
 
 reaction_42 [STAT3] + [Ractive] → [pSTAT3] + [Ractive];   {STAT3} , {Ractive}
 
 reaction_43 [pSTAT3] → [STAT3];   {pSTAT3}
 
 reaction_44 [R_IL6_gp130] → ;   {R_IL6_gp130}
 
 reaction_45 [Ractive] → ;   {Ractive}
 
 mwb675e13a_26c0_4b18_a8c3_0f5a62090ba4 [Ractive] → [R_IL6_gp130];   {Ractive}
 
 mw64df7c9e_35da_4c7f_be56_c5dabfb060b6 [Ractive] → [R_IL6_gp130];   {Ractive}
 
 mw391f3b8e_5649_4851_b2e2_782cb3e015b6  → [gp130];  
 
 mw4a00a3a4_778f_4952_8100_2dc3cc2b7046 [gp130] → ;   {gp130}
 
 mw6db30657_4e56_4c3a_8575_9c67393dde4f  → [gp130];  
 
 mw6f470e13_f0e4_4294_83d8_59dd5670d10c [gp130] → ;   {gp130}
 
 mwfb35eca9_7afc_4ba8_a46c_738cab57eb9f [sR] ↔ [sR];   {sR} , {sR}
 
 mw61d2af92_6da5_41ce_b90e_aa6f430e6ba1 [IL6] ↔ [IL6];   {IL6} , {IL6}
 
 mw4c099d5c_200f_474e_8ec1_59e9223a8afd [sR] + [IL6] ↔ [sR_IL6];   {IL6} , {sR_IL6} , {sR}
 
 mwbe8567ce_3349_4442_8b12_53cd9bc168e7 [sR_IL6] ↔ [sR_IL6];   {sR_IL6} , {sR_IL6}
 
 mw12a9fa7e_a273_4c1e_b970_ed33f3a9a705 [sR] ↔ [sR];   {sR} , {sR}
 
 mw1046000b_e1e8_4f6f_82a1_532d2aa793bb [IL6] ↔ [IL6];   {IL6} , {IL6}
 
 mw8e8b65a8_6830_4091_9a40_19645e8fe554 [sR_IL6] ↔ [sR_IL6];   {sR_IL6} , {sR_IL6}
 
 mwa812f08f_1035_42bd_82d2_72d691308f88 [sR] + [IL6] ↔ [sR_IL6];   {IL6} , {sR} , {sR_IL6}
 
 mwab0012ac_e5f2_4904_9893_820fd210402e [CRP] → [CRPExtracellular];   {CRP}
 
 mwcdc24bd4_d9e4_47fe_8300_d222d853111c [CRP] ↔ [CRPExtracellular];   {CRP} , {CRPExtracellular}
 
 mwff2ebcf1_dcf1_47b9_9cac_7306fc6f7f76  → [CRP];  
 
 mw1c5a5ff7_5130_490f_a740_6a744ccf8a94 [sgp130] ↔ [sgp130];   {sgp130} , {sgp130}
 
 mw7b56053c_7256_4703_a8c3_4fd46b2c23d0 [sgp130] ↔ [sgp130];   {sgp130} , {sgp130}
 
 mw8be158f1_ea81_45bf_80d4_6e31cd83fe6c [sgp130] + [sR_IL6] ↔ [sR_IL6_sgp130];   {sR_IL6_sgp130} , {sR_IL6} , {sgp130}
 
 mwd77df15b_fed7_41a8_a3d6_b0f6c590c5f6 [sR_IL6] + [sgp130] ↔ [sR_IL6_sgp130];   {sgp130} , {sR_IL6} , {sR_IL6_sgp130}
 
 mw01babcdf_0f03_46b0_81b1_201cc846e361 [sR_IL6_sgp130] ↔ [sR_IL6_sgp130];   {sR_IL6_sgp130} , {sR_IL6_sgp130}
 
 mwae5dbb44_7de5_46ab_8c20_ac4f8956b0f0 [sR_IL6_sgp130] ↔ [sR_IL6_sgp130];   {sR_IL6_sgp130} , {sR_IL6_sgp130}
 
 mw432fde6e_59ab_47f0_9fb1_086433a602e3  → [sR];  
 
 mw41c27823_d7ee_4554_9eac_3d5beec8e854 [sR] → ;   {sR}
 
 mw50c6744c_e883_4612_8663_e38750cbad1b  → [sgp130];  
 
 mwb6a99eb5_ea4c_4733_98dd_1daf5ec6b0db [sgp130] → ;   {sgp130}
 
 mw1ce0c484_681f_4d85_8ffe_392d0c100cfa  → [IL6];  
 
 mwf913ea0b_785a_4701_ac91_b18ab5dd5a89 [IL6] → ;   {IL6}
 
 mw71d90b81_8211_4039_8807_12a7fe03206c [CRP] → [sR] + [CRP];   {CRP}
 
 mwdf4ba845_7271_4ada_b43f_fdac83df3b5c [sgpFc] ↔ [sgpFc];   {sgpFc} , {sgpFc}
 
 mwc32a28fa_525c_44af_8d2c_e728c21eb90a [sgpFc] + [sR_IL6] ↔ [sR_IL6_sgpFc];   {sR_IL6} , {sR_IL6_sgpFc} , {sgpFc}
 
 mw14d351b9_623a_48e8_a21c_854411039120 [sR_IL6_sgpFc] → ;   {sR_IL6_sgpFc}
 
 mwba7f4605_8571_439b_b3ab_eb0b43808db8 [sgpFc] → ;   {sgpFc}
 
 mw5be6711a_526a_4a58_80c6_d353dcabdf87 [sR_IL6_sgpFc] → ;   {sR_IL6_sgpFc}
 
 mw1d3068d7_5679_41ee_9892_984e33012070 [sgpFc] + [sR_IL6] ↔ [sR_IL6_sgpFc];   {sR_IL6_sgpFc} , {sR_IL6} , {sgpFc}
 
 mwb341c690_7147_46a1_8577_201598de3bf1 [sgpFc] + [sR_IL6] ↔ [sR_IL6_sgpFc];   {sR_IL6_sgpFc} , {sgpFc} , {sR_IL6}
 
 mw5d9fcd0c_ca08_4444_b509_2ea4777e0025 [sR_IL6_sgpFc] → ;   {sR_IL6_sgpFc}
 
 mw131e3c9d_e77d_48c0_bdbb_77b2c10aaf3d [sgpFc] ↔ [sgpFc];   {sgpFc} , {sgpFc}
 
 mw14940d1f_6a1f_47cb_8170_801ba645f4c1 [sgpFc] ↔ [sgpFc];   {sgpFc} , {sgpFc}
 
 mwb62106e7_e959_4a1d_9a00_b36d4e19a48f [sR_IL6_sgpFc] ↔ [sR_IL6_sgpFc];   {sR_IL6_sgpFc} , {sR_IL6_sgpFc}
 
 mwad648b6c_45ca_4f41_9747_06db1f6060fc [sR_IL6_sgpFc] ↔ [sR_IL6_sgpFc];   {sR_IL6_sgpFc} , {sR_IL6_sgpFc}
 
 mw2ae288ab_7d03_4a84_a024_c711ad2b77e6 [sgpFc] → ;   {sgpFc}
 
 mw9629d028_fcc0_4886_9e4d_36eecdb0381d [sgpFc] → ;   {sgpFc}
 
Rules (3)
 
 Assignment Rule (name: species_1) CRP Suppression (%) = (mw114aa90f_5f5b_4fe8_9406_361c8489b6a1-Metabolite_80)/Metabolite_80/(-100)
 
 Assignment Rule (name: mw0083d743_836f_4238_a17f_4602193d5bc0) geneProduct = mw92d854a7_8aaf_458e_b5e2_20a63ce9b654*mw48867e93_f170_44e8_ac7a_185b23e1bf3b/(mw08950572_81b0_4570_b2e4_b9c3462c1425+mw48867e93_f170_44e8_ac7a_185b23e1bf3b)
 
 Assignment Rule (name: mwd5313618_89eb_4c8c_bc82_66f10f966349) CRP = mw92d854a7_8aaf_458e_b5e2_20a63ce9b654*mw39c2e431_fdc3_4964_be29_6ca856620b1b/(mw08950572_81b0_4570_b2e4_b9c3462c1425+mw39c2e431_fdc3_4964_be29_6ca856620b1b)
 
Events (13)
 
 Week1
sgpFc = mwf345ed7a_0622_403c_b816_c8749a2c9ded+ModelValue_3*2.346
 
 Week2
sgpFc = mwf345ed7a_0622_403c_b816_c8749a2c9ded+ModelValue_3*2.346+ModelValue_4*2.346
 
 Week3
sgpFc = mwf345ed7a_0622_403c_b816_c8749a2c9ded+ModelValue_3*2.346
 
 Week4
sgpFc = mwf345ed7a_0622_403c_b816_c8749a2c9ded+(ModelValue_3+ModelValue_4+ModelValue_5)*2.346
 
 Week5
sgpFc = mwf345ed7a_0622_403c_b816_c8749a2c9ded+ModelValue_3*2.346
 
 Week6
sgpFc = mwf345ed7a_0622_403c_b816_c8749a2c9ded+(ModelValue_3+ModelValue_4)*2.346
 
 Week7
sgpFc = mwf345ed7a_0622_403c_b816_c8749a2c9ded+ModelValue_3*2.346
 
 Week8
sgpFc = mwf345ed7a_0622_403c_b816_c8749a2c9ded+(ModelValue_3+ModelValue_4+ModelValue_5)*2.346
 
 Week9
sgpFc = mwf345ed7a_0622_403c_b816_c8749a2c9ded+ModelValue_3*2.346
 
 Week10
sgpFc = mwf345ed7a_0622_403c_b816_c8749a2c9ded+(ModelValue_3+ModelValue_4)*2.346
 
 Week11
sgpFc = mwf345ed7a_0622_403c_b816_c8749a2c9ded+ModelValue_3*2.346
 
 Week12
sgpFc = mwf345ed7a_0622_403c_b816_c8749a2c9ded+(ModelValue_3+ModelValue_4+ModelValue_5)*2.346
 
 Week0
sgpFc = mwf345ed7a_0622_403c_b816_c8749a2c9ded+ModelValue_3*2.346+ModelValue_4*2.346+ModelValue_5*2.346
 
Functions (50)
 
 Function for reaction_4_4 lambda(kIL6Decay, mw53ffe9e6_beef_45c4_90a5_a79197ed506e, mwf626e95e_543f_41e4_aad4_c6bf60ab345b, kIL6Decay*mwf626e95e_543f_41e4_aad4_c6bf60ab345b/mw53ffe9e6_beef_45c4_90a5_a79197ed506e)
 
 Function for reaction_5_4 lambda(kCRPDecay, mw114aa90f_5f5b_4fe8_9406_361c8489b6a1, mw53ffe9e6_beef_45c4_90a5_a79197ed506e, kCRPDecay*mw114aa90f_5f5b_4fe8_9406_361c8489b6a1/mw53ffe9e6_beef_45c4_90a5_a79197ed506e)
 
 Function for reaction_16_4 lambda(kRAct, mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a, kRAct*mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a/mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e)
 
 Function for reaction_1_4 lambda(kRLOff, kRLOn, mw03db56ac_8dc6_4931_ae82_fef706d2ee3d, mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc, mw53ffe9e6_beef_45c4_90a5_a79197ed506e, mwf626e95e_543f_41e4_aad4_c6bf60ab345b, (kRLOn*mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc*mwf626e95e_543f_41e4_aad4_c6bf60ab345b-kRLOff*mw03db56ac_8dc6_4931_ae82_fef706d2ee3d)/mw53ffe9e6_beef_45c4_90a5_a79197ed506e)
 
 Function for reaction_3_4 lambda(kIL6Synth, mw53ffe9e6_beef_45c4_90a5_a79197ed506e, kIL6Synth/mw53ffe9e6_beef_45c4_90a5_a79197ed506e)
 
 Function for reaction_6_4 lambda(kgp130Off, kgp130On, mw4638f126_8cb8_4021_ab41_6ae195743ba0, mw80848184_e2dd_47ce_86d7_7a21479342bd, mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a, (kgp130On*mw4638f126_8cb8_4021_ab41_6ae195743ba0*mw80848184_e2dd_47ce_86d7_7a21479342bd-kgp130Off*mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a)/mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e)
 
 Function for reaction_46_4 lambda(kRAct, mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9, mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, kRAct*mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9/mwe9501423_9fb4_494b_b5b6_288f3fcb17b5)
 
 Function for reaction_42_4 lambda(mw2b255f94_8018_4b99_bde8_918eeac45446, mw6cce2109_0e32_4dd9_98ec_41173e8ef07d, mw9442cd0e_4d7c_4ba6_a695_f84919bdf569, mwe8fc1900_f07d_468b_b5c8_15400a583c3d, mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, mw9442cd0e_4d7c_4ba6_a695_f84919bdf569*mw6cce2109_0e32_4dd9_98ec_41173e8ef07d*mw2b255f94_8018_4b99_bde8_918eeac45446/(mwe8fc1900_f07d_468b_b5c8_15400a583c3d+mw2b255f94_8018_4b99_bde8_918eeac45446)/mwe9501423_9fb4_494b_b5b6_288f3fcb17b5)
 
 Function for reaction_43_4 lambda(mw48867e93_f170_44e8_ac7a_185b23e1bf3b, mwd36b0261_2480_4cab_9222_2cf8fb0e65dc, mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, mwfd291862_195f_4979_94b5_b4e5ae1b7d52, mwd36b0261_2480_4cab_9222_2cf8fb0e65dc*mw48867e93_f170_44e8_ac7a_185b23e1bf3b/(mwfd291862_195f_4979_94b5_b4e5ae1b7d52+mw48867e93_f170_44e8_ac7a_185b23e1bf3b)/mwe9501423_9fb4_494b_b5b6_288f3fcb17b5)
 
 Function for reaction_44_4 lambda(kRint, mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9, mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, kRint*mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9/mwe9501423_9fb4_494b_b5b6_288f3fcb17b5)
 
 Function for reaction_45_4 lambda(mw6cce2109_0e32_4dd9_98ec_41173e8ef07d, mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, mwf44f7f27_5bb1_4c7f_8964_560fa5e1743a, mwf44f7f27_5bb1_4c7f_8964_560fa5e1743a*mw6cce2109_0e32_4dd9_98ec_41173e8ef07d/mwe9501423_9fb4_494b_b5b6_288f3fcb17b5)
 
 Function for mwb675e13a_26c0_4b18_a8c3_0f5a62090ba4_4 lambda(mw0eb6c959_d408_45a0_a450_928b8c5876bb, mw1667a8e0_9d20_4e59_ba51_596148aba787, mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, mwfcf06900_5f2f_4bb3_bb1f_12023612b8a8, mw1667a8e0_9d20_4e59_ba51_596148aba787*mw0eb6c959_d408_45a0_a450_928b8c5876bb/(mwfcf06900_5f2f_4bb3_bb1f_12023612b8a8+mw0eb6c959_d408_45a0_a450_928b8c5876bb)/mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e)
 
 Function for mw64df7c9e_35da_4c7f_be56_c5dabfb060b6_4 lambda(mw1667a8e0_9d20_4e59_ba51_596148aba787, mw6cce2109_0e32_4dd9_98ec_41173e8ef07d, mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, mwfcf06900_5f2f_4bb3_bb1f_12023612b8a8, mw1667a8e0_9d20_4e59_ba51_596148aba787*mw6cce2109_0e32_4dd9_98ec_41173e8ef07d/(mwfcf06900_5f2f_4bb3_bb1f_12023612b8a8+mw6cce2109_0e32_4dd9_98ec_41173e8ef07d)/mwe9501423_9fb4_494b_b5b6_288f3fcb17b5)
 
 Function for mw391f3b8e_5649_4851_b2e2_782cb3e015b6_4 lambda(kRsynth, mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, kRsynth/mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e)
 
 Function for mw4a00a3a4_778f_4952_8100_2dc3cc2b7046_4 lambda(kRdeg, mw80848184_e2dd_47ce_86d7_7a21479342bd, mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, kRdeg*mw80848184_e2dd_47ce_86d7_7a21479342bd/mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e)
 
 Function for reaction_2_4 lambda(kgp130Off, kgp130On, mw03db56ac_8dc6_4931_ae82_fef706d2ee3d, mw53ffe9e6_beef_45c4_90a5_a79197ed506e, mw810ff751_fa4e_4143_bd50_169b3e325e1e, mwbbbce920_e8dd_4320_9386_fc94bfb2fc99, (kgp130On*mw03db56ac_8dc6_4931_ae82_fef706d2ee3d*mwbbbce920_e8dd_4320_9386_fc94bfb2fc99-kgp130Off*mw810ff751_fa4e_4143_bd50_169b3e325e1e)/mw53ffe9e6_beef_45c4_90a5_a79197ed506e)
 
 Function for reaction_7_4 lambda(kRLOff, kRLOn, mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1, mw10315fa3_6f13_4618_bda8_a8694bd3c374, mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83, mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, (kRLOn*mw10315fa3_6f13_4618_bda8_a8694bd3c374*mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1-kRLOff*mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83)/mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e)
 
 Function for mw6db30657_4e56_4c3a_8575_9c67393dde4f_4 lambda(kRsynth, mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, kRsynth/mwe9501423_9fb4_494b_b5b6_288f3fcb17b5)
 
 Function for mw6f470e13_f0e4_4294_83d8_59dd5670d10c_4 lambda(kRdeg, mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca, mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, kRdeg*mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca/mwe9501423_9fb4_494b_b5b6_288f3fcb17b5)
 
 Function for mw4c099d5c_200f_474e_8ec1_59e9223a8afd_4 lambda(kRLOff, kRLOn, mw2c9b0499_3325_4394_8af3_bbf653a944a0, mw7becb5fe_8da8_4285_a821_0d77ad811b62, mwd31f52cc_04e7_40e0_885f_c7b2d9e62215, mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, (kRLOn*mwd31f52cc_04e7_40e0_885f_c7b2d9e62215*mw2c9b0499_3325_4394_8af3_bbf653a944a0-kRLOff*mw7becb5fe_8da8_4285_a821_0d77ad811b62)/mwe9501423_9fb4_494b_b5b6_288f3fcb17b5)
 
 Function for mwa812f08f_1035_42bd_82d2_72d691308f88_4 lambda(kRLOff, kRLOn, mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1, mw2e464cf3_a09c_4b7c_9f3c_06720016a48e, mw4638f126_8cb8_4021_ab41_6ae195743ba0, mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, (kRLOn*mw2e464cf3_a09c_4b7c_9f3c_06720016a48e*mw0adf3eb4_a196_4c48_b10d_4e9e9faaf9e1-kRLOff*mw4638f126_8cb8_4021_ab41_6ae195743ba0)/mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e)
 
 Function for mwab0012ac_e5f2_4904_9893_820fd210402e_4 lambda(mw862f1480_c60c_4863_a565_b2c1c77e238e, mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, mwd5313618_89eb_4c8c_bc82_66f10f966349, mw862f1480_c60c_4863_a565_b2c1c77e238e*mwd5313618_89eb_4c8c_bc82_66f10f966349/mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e)
 
 Function for mwff2ebcf1_dcf1_47b9_9cac_7306fc6f7f76_4 lambda(mw53ffe9e6_beef_45c4_90a5_a79197ed506e, mw65c85954_5ca0_4df2_9e22_ff2aa3fbe3f1, mw65c85954_5ca0_4df2_9e22_ff2aa3fbe3f1/mw53ffe9e6_beef_45c4_90a5_a79197ed506e)
 
 Function for reaction_8_4 lambda(kgp130Off, kgp130On, mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83, mw80848184_e2dd_47ce_86d7_7a21479342bd, mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a, (kgp130On*mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83*mw80848184_e2dd_47ce_86d7_7a21479342bd-kgp130Off*mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a)/mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e)
 
 Function for reaction_11_4 lambda(kRint, mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83, mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, kRint*mw7d86cc23_a1af_44c3_bdb9_71e9b1bb2a83/mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e)
 
 Function for reaction_12_4 lambda(kRint, mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a, kRint*mwd2d9d93a_3bd1_4f17_bac1_baba9ef2d55a/mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e)
 
 Function for reaction_13_4 lambda(mw0eb6c959_d408_45a0_a450_928b8c5876bb, mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, mwf44f7f27_5bb1_4c7f_8964_560fa5e1743a, mwf44f7f27_5bb1_4c7f_8964_560fa5e1743a*mw0eb6c959_d408_45a0_a450_928b8c5876bb/mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e)
 
 Function for reaction_14_4 lambda(kRsynth, mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, kRsynth/mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e)
 
 Function for reaction_41_4 lambda(kgp130Off, kgp130On, mw7becb5fe_8da8_4285_a821_0d77ad811b62, mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9, mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca, mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, (kgp130On*mw7becb5fe_8da8_4285_a821_0d77ad811b62*mw8c9107e6_f51d_442d_b2dc_2bfdbb8482ca-kgp130Off*mw824bc3d4_1ac3_4912_9b51_8f14ff1c96b9)/mwe9501423_9fb4_494b_b5b6_288f3fcb17b5)
 
 Function for mw14d351b9_623a_48e8_a21c_854411039120_3 lambda(mw53ffe9e6_beef_45c4_90a5_a79197ed506e, mwa2d8dd1c_bb9a_4552_8738_e24671651c1d, mwbd1d5bc3_d4b9_4aec_9b86_6f776da20a30, mwbd1d5bc3_d4b9_4aec_9b86_6f776da20a30*mwa2d8dd1c_bb9a_4552_8738_e24671651c1d/mw53ffe9e6_beef_45c4_90a5_a79197ed506e)
 
 Function for mwba7f4605_8571_439b_b3ab_eb0b43808db8_4 lambda(mw53ffe9e6_beef_45c4_90a5_a79197ed506e, mwbd1d5bc3_d4b9_4aec_9b86_6f776da20a30, mwf345ed7a_0622_403c_b816_c8749a2c9ded, mwbd1d5bc3_d4b9_4aec_9b86_6f776da20a30*mwf345ed7a_0622_403c_b816_c8749a2c9ded/mw53ffe9e6_beef_45c4_90a5_a79197ed506e)
 
 Function for mw5be6711a_526a_4a58_80c6_d353dcabdf87_3 lambda(mw2f3d48e0_c9c4_4a0e_aca3_9241eb573296, mwbd1d5bc3_d4b9_4aec_9b86_6f776da20a30, mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, mwbd1d5bc3_d4b9_4aec_9b86_6f776da20a30*mw2f3d48e0_c9c4_4a0e_aca3_9241eb573296/mwe9501423_9fb4_494b_b5b6_288f3fcb17b5)
 
 Function for mw1d3068d7_5679_41ee_9892_984e33012070_1 lambda(kgp130Off, kgp130On, mw2f3d48e0_c9c4_4a0e_aca3_9241eb573296, mw7becb5fe_8da8_4285_a821_0d77ad811b62, mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, mwf7796221_1fea_4274_a93e_c00adbf5778c, (kgp130On*mwf7796221_1fea_4274_a93e_c00adbf5778c*mw7becb5fe_8da8_4285_a821_0d77ad811b62-kgp130Off*mw2f3d48e0_c9c4_4a0e_aca3_9241eb573296)/mwe9501423_9fb4_494b_b5b6_288f3fcb17b5)
 
 Function for mwb341c690_7147_46a1_8577_201598de3bf1_1 lambda(kgp130Off, kgp130On, mw1d9426a3_e1e9_49e0_ad77_eb6833be398a, mw3667a5e1_02c9_44a0_acb4_b0431faa822d, mw4638f126_8cb8_4021_ab41_6ae195743ba0, mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, (kgp130On*mw3667a5e1_02c9_44a0_acb4_b0431faa822d*mw4638f126_8cb8_4021_ab41_6ae195743ba0-kgp130Off*mw1d9426a3_e1e9_49e0_ad77_eb6833be398a)/mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e)
 
 Function for mw5d9fcd0c_ca08_4444_b509_2ea4777e0025_3 lambda(mw1d9426a3_e1e9_49e0_ad77_eb6833be398a, mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, mwbd1d5bc3_d4b9_4aec_9b86_6f776da20a30, mwbd1d5bc3_d4b9_4aec_9b86_6f776da20a30*mw1d9426a3_e1e9_49e0_ad77_eb6833be398a/mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e)
 
 Function for mw2ae288ab_7d03_4a84_a024_c711ad2b77e6_4 lambda(mw3667a5e1_02c9_44a0_acb4_b0431faa822d, mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, mwbd1d5bc3_d4b9_4aec_9b86_6f776da20a30, mwbd1d5bc3_d4b9_4aec_9b86_6f776da20a30*mw3667a5e1_02c9_44a0_acb4_b0431faa822d/mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e)
 
 Function for mw9629d028_fcc0_4886_9e4d_36eecdb0381d_4 lambda(mwbd1d5bc3_d4b9_4aec_9b86_6f776da20a30, mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, mwf7796221_1fea_4274_a93e_c00adbf5778c, mwbd1d5bc3_d4b9_4aec_9b86_6f776da20a30*mwf7796221_1fea_4274_a93e_c00adbf5778c/mwe9501423_9fb4_494b_b5b6_288f3fcb17b5)
 
 Function for mw8be158f1_ea81_45bf_80d4_6e31cd83fe6c_4 lambda(kgp130Off, kgp130On, mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3, mw7becb5fe_8da8_4285_a821_0d77ad811b62, mwd65b5b39_dc1b_4e77_a999_67277a880e5e, mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, (kgp130On*mwd65b5b39_dc1b_4e77_a999_67277a880e5e*mw7becb5fe_8da8_4285_a821_0d77ad811b62-kgp130Off*mw6335d5d7_c7b0_4bc0_b883_f7ee4915c2c3)/mwe9501423_9fb4_494b_b5b6_288f3fcb17b5)
 
 Function for mwd77df15b_fed7_41a8_a3d6_b0f6c590c5f6_4 lambda(kgp130Off, kgp130On, mw147d30ec_478e_4090_b496_128a131d29eb, mw4638f126_8cb8_4021_ab41_6ae195743ba0, mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, mwab41493c_6349_45f1_a226_3030cfed0e06, (kgp130On*mw4638f126_8cb8_4021_ab41_6ae195743ba0*mw147d30ec_478e_4090_b496_128a131d29eb-kgp130Off*mwab41493c_6349_45f1_a226_3030cfed0e06)/mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e)
 
 Function for mw432fde6e_59ab_47f0_9fb1_086433a602e3_4 lambda(mw53ffe9e6_beef_45c4_90a5_a79197ed506e, mwc4c58db7_5535_4590_aaa5_bbc8ed53cdab, mwc4c58db7_5535_4590_aaa5_bbc8ed53cdab/mw53ffe9e6_beef_45c4_90a5_a79197ed506e)
 
 Function for mw41c27823_d7ee_4554_9eac_3d5beec8e854_4 lambda(mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc, mw53ffe9e6_beef_45c4_90a5_a79197ed506e, mw88a75379_f9a1_4acc_baeb_94c32bb736a5, mw88a75379_f9a1_4acc_baeb_94c32bb736a5*mw30ae63db_6cd3_4b6f_93ad_3350cd360bcc/mw53ffe9e6_beef_45c4_90a5_a79197ed506e)
 
 Function for mw50c6744c_e883_4612_8663_e38750cbad1b_4 lambda(mw1f41474c_c399_4a60_a53a_9926dd092e8d, mw53ffe9e6_beef_45c4_90a5_a79197ed506e, mw1f41474c_c399_4a60_a53a_9926dd092e8d/mw53ffe9e6_beef_45c4_90a5_a79197ed506e)
 
 Function for mwb6a99eb5_ea4c_4733_98dd_1daf5ec6b0db_4 lambda(mw53ffe9e6_beef_45c4_90a5_a79197ed506e, mwbbbce920_e8dd_4320_9386_fc94bfb2fc99, mwbcb5a310_9b67_405e_89ec_43d25e8cc93d, mwbcb5a310_9b67_405e_89ec_43d25e8cc93d*mwbbbce920_e8dd_4320_9386_fc94bfb2fc99/mw53ffe9e6_beef_45c4_90a5_a79197ed506e)
 
 Function for mw1ce0c484_681f_4d85_8ffe_392d0c100cfa_4 lambda(mwa8d72918_f6c2_4d81_bf3b_fc2b464d5e69, mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, mwa8d72918_f6c2_4d81_bf3b_fc2b464d5e69/mwe9501423_9fb4_494b_b5b6_288f3fcb17b5)
 
 Function for mwf913ea0b_785a_4701_ac91_b18ab5dd5a89_4 lambda(mw06241335_b5f2_47ed_bdcc_ef77b68a2b98, mw2c9b0499_3325_4394_8af3_bbf653a944a0, mwe9501423_9fb4_494b_b5b6_288f3fcb17b5, mw06241335_b5f2_47ed_bdcc_ef77b68a2b98*mw2c9b0499_3325_4394_8af3_bbf653a944a0/mwe9501423_9fb4_494b_b5b6_288f3fcb17b5)
 
 Function for mw71d90b81_8211_4039_8807_12a7fe03206c_4 lambda(mw114aa90f_5f5b_4fe8_9406_361c8489b6a1, mw53ffe9e6_beef_45c4_90a5_a79197ed506e, mw5832a2dc_ee18_44df_aa59_ccb21cb74df2, mw5832a2dc_ee18_44df_aa59_ccb21cb74df2*mw114aa90f_5f5b_4fe8_9406_361c8489b6a1/mw53ffe9e6_beef_45c4_90a5_a79197ed506e)
 
 Function for mwc32a28fa_525c_44af_8d2c_e728c21eb90a_1 lambda(kgp130Off, kgp130On, mw03db56ac_8dc6_4931_ae82_fef706d2ee3d, mw53ffe9e6_beef_45c4_90a5_a79197ed506e, mwa2d8dd1c_bb9a_4552_8738_e24671651c1d, mwf345ed7a_0622_403c_b816_c8749a2c9ded, (kgp130On*mwf345ed7a_0622_403c_b816_c8749a2c9ded*mw03db56ac_8dc6_4931_ae82_fef706d2ee3d-kgp130Off*mwa2d8dd1c_bb9a_4552_8738_e24671651c1d)/mw53ffe9e6_beef_45c4_90a5_a79197ed506e)
 
 Function for reaction_9_4 lambda(mw0eb6c959_d408_45a0_a450_928b8c5876bb, mw42054cd7_17af_46da_970c_7f99151906ad, mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, mw9442cd0e_4d7c_4ba6_a695_f84919bdf569, mwe8fc1900_f07d_468b_b5c8_15400a583c3d, mw9442cd0e_4d7c_4ba6_a695_f84919bdf569*mw0eb6c959_d408_45a0_a450_928b8c5876bb*mw42054cd7_17af_46da_970c_7f99151906ad/(mwe8fc1900_f07d_468b_b5c8_15400a583c3d+mw42054cd7_17af_46da_970c_7f99151906ad)/mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e)
 
 Function for reaction_10_4 lambda(mw39c2e431_fdc3_4964_be29_6ca856620b1b, mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, mwd36b0261_2480_4cab_9222_2cf8fb0e65dc, mwfd291862_195f_4979_94b5_b4e5ae1b7d52, mwd36b0261_2480_4cab_9222_2cf8fb0e65dc*mw39c2e431_fdc3_4964_be29_6ca856620b1b/(mwfd291862_195f_4979_94b5_b4e5ae1b7d52+mw39c2e431_fdc3_4964_be29_6ca856620b1b)/mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e)
 
 Function for reaction_15_4 lambda(kRdeg, mw10315fa3_6f13_4618_bda8_a8694bd3c374, mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e, kRdeg*mw10315fa3_6f13_4618_bda8_a8694bd3c374/mw88ca8d9a_f5cf_41bf_9d9d_fc48f6e1a19e)
 
 serum Spatial dimensions: 3.0  Compartment size: 1.0
 
 IL6
Compartment: serum
Initial amount: 4.35628896551166E-4
 
 sgp130
Compartment: serum
Initial amount: 3.9
 
 sR_IL6_sgp130
Compartment: serum
Initial amount: 0.0874060669217432
 
 CRP
Compartment: serum
Initial amount: 221.06367608557
 
 sR
Compartment: serum
Initial amount: 4.25350679194445
 
 sR_IL6
Compartment: serum
Initial amount: 0.00109424263781451
 
 sgpFc
Compartment: serum
Initial amount: -1.22575436720674E-26
 
 sR_IL6_sgpFc
Compartment: serum
Initial amount: -2.29473714389906E-28
 
  CRP Suppression (%)
Compartment: serum
Initial concentration: 0.0
 
 liver Spatial dimensions: 3.0  Compartment size: 1.0
 
 gp130
Compartment: liver
Initial amount: 0.388958921403941
 
 R_IL6_gp130
Compartment: liver
Initial amount: 6.59935877686372E-5
 
 sR_IL6
Compartment: liver
Initial amount: 9.76164943878913E-4
 
 R
Compartment: liver
Initial amount: 0.438235811135574
 
 IL6
Compartment: liver
Initial amount: 7.2566581144648E-4
 
 R_IL6
Compartment: liver
Initial amount: 1.60036523605187E-5
 
 Ractive
Compartment: liver
Initial amount: 0.765416493681823
 
 STAT3
Compartment: liver
Initial amount: 0.777537339578334
 
 pSTAT3
Compartment: liver
Initial amount: 9.22246266042167
 
  CRP
Compartment: liver
Initial amount: 158.325846781611
 
 sR
Compartment: liver
Initial amount: 6.08704712819468
 
 CRPExtracellular
Compartment: liver
Initial amount: 409.775322370541
 
 sgp130
Compartment: liver
Initial amount: 5.5896988923534
 
 sR_IL6_sgp130
Compartment: liver
Initial amount: 0.116343661809953
 
 sR_IL6_sgpFc
Compartment: liver
Initial amount: -1.68120955431364E-27
 
 sgpFc
Compartment: liver
Initial amount: -6.97919693038973E-26
 
   gut Spatial dimensions: 3.0  Compartment size: 1.0
 
 sR_IL6
Compartment: gut
Initial amount: 0.00130682388893128
 
 gp130
Compartment: gut
Initial amount: 0.374962692933961
 
 R_IL6_gp130
Compartment: gut
Initial amount: 8.44890497633548E-5
 
 Ractive
Compartment: gut
Initial amount: 0.980272509547246
 
 STAT3
Compartment: gut
Initial amount: 0.610636013508212
 
 pSTAT3
Compartment: gut
Initial amount: 9.38936398649179
 
  geneProduct
Compartment: gut
Initial amount: 159.80359735889
 
 sR
Compartment: gut
Initial amount: 6.06410682471754
 
 IL6
Compartment: gut
Initial amount: 0.0093481986616084
 
 sgp130
Compartment: gut
Initial amount: 5.56973864471412
 
 sR_IL6_sgp130
Compartment: gut
Initial amount: 0.136303909449242
 
 sgpFc
Compartment: gut
Initial amount: -5.46278871281916E-28
 
 sR_IL6_sgpFc
Compartment: gut
Initial amount: 5.3253664019487E-28
 
 peripheral Spatial dimensions: 3.0  Compartment size: 1.0
 
 sgpFc
Compartment: peripheral
Initial amount: -6.85083014757454E-27
 
Global Parameters (53)
 
   kRLOn
Value: 0.384
Constant
 
   kRLOff
Value: 1.92
Constant
 
 kgp130On
Value: 20.52
Constant
 
   kgp130Off
Value: 1.026
Constant
 
   kRAct
Value: 155.0
Constant
 
 kRint
Value: 1.96
Constant
 
   kRsynth
Value: 0.0685
Constant
 
 kRintBasal
Value: 0.1561
Constant
 
   ksynthIL6
Value: 0.0063
Constant
 
 kdegIL6
Value: 34.82
Constant
 
   kdegCRP
Value: 0.36
Constant
 
   KmSTATDephos
Value: 5.34
Constant
 
   VmSTATDephos
Value: 0.62
Constant
 
 VmRDephos
Value: 0.525
Constant
 
   KmRDephos
Value: 155.3
Constant
 
 kcatSTATPhos
Value: 145.0
Constant
 
   KmSTATPhos
Value: 219.0
Constant
 
   KmProtSynth
Value: 10.0
Constant
 
 VmProtSynth
Value: 330.0
Constant
 
   kCRPSecretion
Value: 0.5
Constant
 
 ksynthCRP
Value: 0.42
Constant
 
   ksynthsR
Value: 0.1
Constant
 
   kdegsR
Value: 0.3
Constant
 
   ksynthsgp130
Value: 3.9
Constant
 
 kdegsgp130
Value: 1.0
Constant
 
   ksynthIL6Gut
Value: 0.036
Constant
 
   kdegIL6Gut
Value: 1.0
Constant
 
   kdistTissueToSerum
Value: 0.8473
Constant
 
 kdistSerumToTissue
Value: 1.2125
Constant
 
   kRShedding
Value: 0.0054
Constant
 
   kintActiveR
Value: 0.01
Constant
 
   infusionTime
Value: 1.0
Constant
 
   kAbSerumToLiver
Value: 0.0208333333333333
Constant
 
   kAbLiverToSerum
Value: 0.0208333333333333
Constant
 
   kAbSerumToGut
Value: 0.0104166666666667
Constant
 
   kAbGutToSerum
Value: 0.0208333333333333
Constant
 
   VSerum
Value: 2.88
Constant
 
   VLiver
Value: 2.88
Constant
 
   VGut
Value: 1.44
Constant
 
   VPeriph
Value: 0.576
Constant
 
   QSerumLiver
Value: 0.06
Constant
 
   QSerumGut
Value: 0.03
Constant
 
   QSerumPeriph
Value: 0.001
Constant
 
 kAbSerumToPeriph
Value: 3.47222222222222E-4
Constant
 
   kAbPeriphToSerum
Value: 0.00173611111111111
Constant
 
   kdegAb
Value: 0.0018
Constant
 
 Dose Q1W
Constant
 
 Dose Q2W
Constant
 
 Dose Q4W
Constant
 
 Initial for CRP
Value: 221.06367608557
Constant
 
 Initial for Dose Q1W
Constant
 
 Initial for Dose Q2W
Constant
 
 Initial for Dose Q4W
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000536

Curator's comment: (updated: 06 Aug 2014 12:29:53 GMT)

Figure 6b: Suppression of CRP after 12 weeks of sgp130Fc administration. Separate curves represent timing between doses.
sgp130Fc is an antibody modified with sgp130, an endogenous Inhibitor and sequestration glycoprotein of the IL6/IL6Ra soluble complex.

Three separate simulations, one for each dose regimen, were carried out by parameter scan for Dose with 8 intervals between 0 and 2000 mg. Results plotted in libreCalc.

Additional file(s)
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