The development of the Psycho-Neuro-Endocrine-Immunology (P.N.E.I.), induced a fundamental paradigm shift in the interpretation of the biological functions of the body; from a separatist point of view to an unifying one, centered on the recognized importance of the cross-talk between cells, organs and systems. This interplay is regulated by a great number of messenger molecules and their circulating levels are key parameters for the definition of both physiological and pathological conditions; indeed, the pathological phenomenon can be described as an imbalance in intercellular signaling. The restoration of the impaired signalling molecules balance is the goal of Low Dose Medicine (LDM), a new medical approach based on the administration of low physiological doses of messenger molecules (which act as homeostatic modulating agents). The validity of the Low Dose Medicine conceptual approach in terms of efficacy and safety is assessed by five years of scientific research in this field. In particular the role of low dose Sequential Kinetic Activation (SKA) signalling molecules oral administration in inflammatory status management is demonstrated.