title: Assessing cytokines' talking patterns following experimental myocardial damage by applying Shannon's information theory.
abstract: BACKGROUND
  The simultaneous measurement of multiple cytokines in parallel by using multiplex proteome arrays (MPA) is of great interest to understanding the inflammatory response following myocardial infarction; however, since cytokines are pleiotropic and redundant, increase of information throughput (IT) attained by measuring multiple cytokines remain to be determined. We aimed this study to assess the IT of an MPA system designed to assess 8 cytokines - commercially available at the time of the study - serum levels, before (control state) and after experimental myocardial cryoinjury (activated state) in rats.
  
  
  METHODS
  By assuming that redundant information do not generally increase the IT, we derived Entropy (H) and Redundancy (R) of information by using formulas of Shannon modified accordingly, where a high IT (high H and low R) corresponds to a low level of correlation between cytokines and vice versa for a low IT. The maximum theoretical level of IT and the contribution of each cytokine were also estimated.
  
  
  RESULTS
  In control state, no significant correlations were found between cytokines showing high IT; on the contrary, in activated state, several significant correlations were found supporting a complex cross-talk pattern between cytokines with low IT. Using as reference the maximum theoretical level of IT, in activated state, H was reduced of 67.0% and R was increased of 77.4% supporting a reduction of IT. Furthermore, the contribution of individual cytokines to H value of MPA was variable: in control state, IL-2 gave the most contribution to H value, conversely during activated state IL-10 gave most contribution. Finally during activated state, IL-1β was the only cytokine strongly correlated with values of all other cytokines, suggesting a crucial role in the inflammatory cascade.
  
  
  CONCLUSIONS
  Paradoxically, by analyzing an MPA system designed for redundant analytes such as cytokines, translating the Shannon's information theory from the field of communication to biology, the IT system in our model deteriorates during the activation state by increasing its redundancy, showing maximum value of entropy in the control conditions. Finally, the study of the mutual interdependence between cytokines by the contribution to the IT may allow formulating alternative models to describe the inflammatory cascade after myocardial infarction.
authors.affiliation: Department of Clinical Science and Community Health, Laboratory of Clinical Informatics and Cardiovascular Imaging, University of Milan, 20122 Milan, Italy. Electronic address: michele.ciulla@unimi.it.
authors.forename: Michele M
authors.initials: MM
authors.lastname: Ciulla
authors.affiliation: Cardiology 1, Emodinamica, Ospedale Niguarda Ca' Granda, Milan, Italy. Electronic address: federico.demarco@gmail.com.
authors.forename: Federico
authors.initials: F
authors.lastname: De Marco
authors.affiliation: Cell Factory "Franco Calori", Milan, Italy; Foundation I.R.C.C.S. Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy. Electronic address: ely.mega@gmail.com.
authors.forename: Elisa
authors.initials: E
authors.lastname: Montelatici
authors.affiliation: Cell Factory "Franco Calori", Milan, Italy; Foundation I.R.C.C.S. Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy. Electronic address: lorenza.lazzari@policlinico.mi.it.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Lazzari
authors.affiliation: Department of Clinical Science and Community Health, Laboratory of Clinical Informatics and Cardiovascular Imaging, University of Milan, 20122 Milan, Italy. Electronic address: gianluca.perrucci@unimi.it.
authors.forename: Gianluca L
authors.initials: GL
authors.lastname: Perrucci
authors.affiliation: Department of Clinical Science and Community Health, Laboratory of Clinical Informatics and Cardiovascular Imaging, University of Milan, 20122 Milan, Italy; Foundation I.R.C.C.S. Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy. Electronic address: fabio.magrini@unimi.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Magrini
mesh_terms: D000818:Animals; D002450:Cell Communication; D016207:Cytokines / Q000097:blood*; D019277:Entropy; D006801:Humans; D007257:Information Theory; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D049490:Systems Biology
chemical_list: D016207:Cytokines
keywords: Cryoinjury; Cytokines cross talk; Entropy; Redundancy