The TH1 and TH2 cytokine network in healthy subjects: Suggestions for experimental studies to create prognostic and diagnostic indices for biotherapeutic treatments

In vivo and in vitro studies have demonstrated the selective regulatory eff ect that TH1 and TH2 cytokines reciprocally exert in the regulation of the polarization of precursor cells into TH1 or TH2 types. The study of the net work relationships between TH1 and TH2 (TH1/TH2) cytokines in healthy subje cts could lead to a better understanding of how the physiological network o f cytokines regulates the immune response. Such study could lead to gain su ggestions for follow-up experiments to create prognostic and diagnostic ind ices for biotherapeutic treatments of patients. Hence we determined serum l evels (environment network) and PBMC production (cellular network) of IL2, IFN gamma, IL5, IL6 and ILIO in the peripheral blood of healthy subjects; t hese cytokines made up our networks under basic conditions. Both men and wo men were studied as hormones can influence the polarization of TH1 and TH2 cells. Cytokines within the physiological network function simultaneously s o multivariate statistical methods were used to study TH1/TH2 relationships . The use of mathematical modelling is the only effective way of studying t he immune system as a whole. The physiological TH1/TH2 network under activa tion conditions was evaluated by incorporating: sIL2R and sIL6R into the ba sic environment network model and the production levels of cytokines by PBM C after PHA stimulus, into the basic cellular network model. The influence of APC was evaluated by adding: serum levels of TNF alpha and IL1 beta to t he environment network model, and production levels of IFN gamma, ILIO and IL6, after stimulus with LPS, to the cellular network model. Our results le d us to hypothesize that the physiological network of TH1/TH2 cytokines reg ulates TH polarization by means of specific relationships between TH1 and T H2 cytokines, which may be different in men and women. These relationships could be studied experimentally to create prognostic and diagnostic indices for more efficient prevention programs and biotherapeutic treatments of pa tients.