Since the 1970s, research studies in the fields of Physiology and Molecular Biology have highlighted the critical role of signaling molecules in all physiological and pathological processes. It is acknowledged that these substances play a decisive role in determining a state of health or illness, and it is now established that every disease is the expression of an altered concentration, i.e. an excess or a deficiency, of these substances. Many international medical research studies are focused on studying signaling molecules and their role in determining the positive (healing) or negative (progression) evolution of a great number of pathological conditions, and therefore the possibility of using them for therapeutic purposes.

Moreover, in the last years the medical field has undergone a gradual shift from the separatist and scotomized vision of body’s biological functions, giving way to a more unified vision, according to the guiding principles of Psycho-Neuro-Endocrine-Immunology (P.N.E.I.) [1–4]. The P.N.E.I. approach represents a real paradigm shift in Medicine: from a strictly biomedical and specialized view of health and disease to a deeply interdisciplinary one. The key for understanding the P.N.E.I. approach is the cross-talk between the psycho-neuro-endocrine systems and the immune system.

Figure 1:
P.N.E.I. network and bi-directional cross-talk between the systems.

This sophisticated cross-talk [14–16] is mediated by a complex network of signaling molecules:

• cytokines
• hormones
• neuropeptides
• growth factors

These are the vehicle of the biological information necessary for such a complex and efficient regulation of cellular responses to stimuli. An altered cross-talk due to an imbalance between specific signaling molecules is fundamental, for example, in the onset of inflammatory, allergic and autoimmune diseases [5–7]. Restoring the physiological concentration of signaling molecules is the key point to recover the homeostatic balance.

Homeostatic Conditions
In homeostatic conditions (corresponding to a healthy state), the concentrations of these molecules in the extra-cellular matrix (ECM) [8–9, 17–18] are comprised in a specific physiological range (from nanograms/ml to picograms/ml) [19–20] and diseases can be considered as expressions and consequences of an altered concentration of these fundamental substances [10–13].

Figure 2:
Range of physiological concentration of signaling molecules at the level of the extracellular matrix.

The signaling molecules used in LDM are orally administered and their activity is systemic (working on complex cell signaling pathways). Scientific literature reports that cytokine oral intake is effective in modulating immune response [21–24] and that a possible action mechanism involves M cells at the level of intestinal epithelium.