How to Monitor the Neuroimmune Biological Response in Patients Affected by Immune Alteration-Related Systemic Diseases

  • Paolo Lissoni
  • Franco Rovelli
  • Luigi Vigorè
  • Giusy Messina
  • Arianna Lissoni
  • Giorgio Porro
  • Giuseppe Di Fede
Part of the Methods in Molecular Biology book series (MIMB, volume 1781)


The clinical management of patients affected by systemic diseases, including cancer and autoimmune diseases, is generally founded on the evaluation of the only markers related to the single disease rather than the biological immuno-inflammatory response of patients, despite the fundamental role of cytokine network in the pathogenesis of cancer and autoimmunity is well known. Cancer progression has appeared to be associated with a progressive decline in the blood levels of the main antitumor cytokines, including IL-2 and IL-12, in association with an increase in those of inflammatory cytokines, including IL-6, TNF-alpha, and IL-1-beta, and immunosuppressive cytokines, namely TGF-beta and IL-10. On the other hand, the severity of the autoimmune diseases has been proven to be greater in the presence of high blood levels of IL-17, TNF-alpha, IL-6, IL-1-beta, IFN-gamma, and IL-18, in association with low levels of TGF-beta and IL-10. However, because of excessive cost and complexity of analyzing the data regarding the secretion of the single cytokines, the relation between lymphocyte-induced immune activation and monocyte-macrophage-mediated immunosuppression has been recently proven to be expressed by the simple lymphocyte-to-monocyte ratio (LMR). The evidence of low LMR values has appeared to correlate with a poor prognosis in cancer and with a disease control in the autoimmune diseases. Moreover, since the in vivo immunoinflammatory response is physiologically under a neuroendocrine modulation, for the evaluation of patient biological response it would be necessary to investigate the function of at least the two main neuroendocrine structures involved in the neuroendocrine modulation of the immune responses, consisting of the hypothalamic-pituitary-adrenal axis and the pineal gland, since the lack of physiological circadian rhythm of cortisol and pineal hormone melatonin has appeared to be associated with a worse prognosis in the human systemic diseases.

Key words

Autoimmunity Biological response Cancer Cannabinoid system Cytokine network Immunotherapy Lymphocyte-to-monocyte ratio Melatonin Neuroimmunomodulation Opioid system Pineal gland Synchronization 


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Paolo Lissoni
    • 1
  • Franco Rovelli
    • 1
  • Luigi Vigorè
    • 1
  • Giusy Messina
    • 1
  • Arianna Lissoni
    • 1
  • Giorgio Porro
    • 1
  • Giuseppe Di Fede
    • 1
  1. 1.Institute of Biological MedicineMilanItaly

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