The Fascination of Cytokine Immunological Science
Paolo Lissoni, Giusy Messina, F. Pelizzoni, Franco Rovelli, Fernando Brivio, Alejandra Monzon, Nadal Crivelli, Arianna Lissoni, Simonetta Tassoni, Andrea Sassola, Sonja Pensato, Giuseppe Di Fede
Abstract
Today, it is known that all human biological functions are under two fundamental regulatory systems, consisting of the endocrine system and the cytokine network. Moreover, it has been shown that the cytokines released from the activated immune cells do not influence only immune functions, but also the whole biological system, including the various metabolic activities, the cardiovascular system, and the functionless of the neuroendocrine system itself. Unfortunately, despite the well-demonstrated importance of cytokines in maintaining the status of health, from a clinical point of view the routine evaluation of the cytokine system still remains unconsidered to establish the status of health, since it is investigated only in severe conditions, such as septic shock, disseminated intravascular coagulation and respiratory distress, which have been demonstrated to be due to an abnormal endogenous production of inflammatory cytokines, namely IL-6, TNF-alpha, and IL-1 beta. This clinical deficiency was depended on several factors, particularly on the complexity of cytokine interactions themselves, but also on the decision to use artificial molecules, such as monoclonal antibodies against the various cytokines, to counteract their eventual abnormally enhanced endogenous production, rather than to investigate the mechanisms responsible for their altered production and to correct eventual alterations. The main reason of the complexity of the cytokine network is related to the fact that the interactions occurring among the different cytokines are often founded on positive feedback mechanisms, then on reciprocal stimulatory actions, while the endocrine system is substantially based on negative feedback circuits. The aim of the present review is to propose a synthetic knowledge regarding the main effects and the source of origin of each single interleukin discovered up to now, to elaborate a first preliminary fundamental physiology of the cytokine network.