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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
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1781)

Abstract

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 

References

  1. 1.
    Rubinow DR (1987) Brain, behaviour and immunity: an interactive system. J Natl Cancer Invest Monogr 10:79–82Google Scholar
  2. 2.
    Zou W (2006) Regulatory T cells, tumor immunity and immunotherapy. Nat Rev Immunol 6:295–307CrossRefPubMedGoogle Scholar
  3. 3.
    Antony MH (2003) Psychoneuroimmunology of cancer. Brain Behav Immun 17:84–91CrossRefGoogle Scholar
  4. 4.
    Besedovsky HO, Sorkin E, Muller I (1975) Hormonal changes during immune response. Proc Soc Exp Biol Med 150:466–471CrossRefPubMedGoogle Scholar
  5. 5.
    Lissoni P, Resentini M, Mauri R et al (1986) Effects of tetrahydrocannabinol on melatonin secretion in man. Horm Metab Res 18:77–78CrossRefPubMedGoogle Scholar
  6. 6.
    Mestroni GJM (1993) The immunoneuronedocrine role of melatonin. J Pineal Res 14:1–10CrossRefGoogle Scholar
  7. 7.
    Brzezinski A (1997) Melatonin in humans. N Engl J Med 336:186–195CrossRefPubMedGoogle Scholar
  8. 8.
    Banks RE, Patel PM, Selby PJ (1995) Interleukin-12: a new clinical player in cytokine therapy. Br J Cancer 71:655–659CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Grimm EA, Mazumder A, Zhang HZ et al (1982) Lymphokine-activated killer cell phenomenon. J Exp Med 155:1823–1841CrossRefPubMedGoogle Scholar
  10. 10.
    Mantovani A, Allavena P, Sica A et al (2008) Cancer-related inflammation. Nature 454:436–444CrossRefPubMedGoogle Scholar
  11. 11.
    Kim R, Emi M, Tanabe K et al (2004) The role of Fas ligand and transfroming growth factor beta in tumor progression. Cancer 100:2281–2291CrossRefPubMedGoogle Scholar
  12. 12.
    Manfredi B, Sacerdote P, Bianchi M (1993) Evidence for an opioid inhibitory tone on T cell proliferation. J Neuroimmunol 44:43–46CrossRefPubMedGoogle Scholar
  13. 13.
    Grotehnermen F (2004) Pharmacology of cannabinoids. Neuroendocrinol Lett 25:14–23Google Scholar
  14. 14.
    Aswell S, Janetka JW, Zabludoff K (2008) Keeping checkpoin kinase in line: new selective inhibitors in clinical trials. Expert Opin Investig Drugs 17:1331–1340CrossRefGoogle Scholar
  15. 15.
    Chen J, Jiang CC, Jin L, Zhang XD (2016) Regulation of PD-L1: a novel role of pro-survival signaling in cancer. Ann Oncol 27:409–416CrossRefPubMedGoogle Scholar
  16. 16.
    Miller RA (1996) The aging immune system: primer and prospectus. Science 273:70–74CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Riley V (1981) Psychoneuroendocrine influence on immunocompetence and neoplasia. Science 212:1100–1109CrossRefPubMedGoogle Scholar
  18. 18.
    Mormont MC, Levi D (1997) Circadian system alterations during cancer processes: a review. Int J Cancer 70:241–247CrossRefPubMedGoogle Scholar
  19. 19.
    Lissoni P, Messina G, Balestra A et al (2008) Efficacy of cancer chemotherapy in relation to synchronization of cortisol rhythm, immune status and psychospiritual profile in metastatic non-small cell lung cancer. In Vivo 22:257–262PubMedGoogle Scholar
  20. 20.
    Bartsch C, Bartsch H (1999) Melatonin in cancer patients and in tuor-bearing animals. Adv Exp Med Biol 467:247–264CrossRefPubMedGoogle Scholar
  21. 21.
    Brivio F, Fumagalli L, Fumagalli G et al (2010) Synchronization of cortisol circadian rhythm by the pineal hormone melatonin in untreatable metastatic solid tumor patients and its possible prognostic signioficance on tumor progression. In Vivo 24:239–242PubMedGoogle Scholar
  22. 22.
    Lissoni P (1996) Prognostic markers in interleukin-2 therapy. Cancer Biother Radiopharm 11:285–287PubMedGoogle Scholar
  23. 23.
    Fumagalli L, Lissoni P, Di Felice G (1999) Pretreatment serum markers and lymphocyte response to interleukin-2 therapy. Br J Cancer 80:407–411CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Korn T, Bettelli E, Oukka M, Kuchroo VK (2009) IL-17 and Th17 cells. Annu Rev Immunol 27:485–517CrossRefPubMedGoogle Scholar
  25. 25.
    Dinarello CA (2007) Interleukin-18 in the pathogenesis of inflammatory diseases. Semin Nephrol 27:98–114CrossRefPubMedGoogle Scholar
  26. 26.
    Tian Y, Yuan C, Ma D et al (2011) IL-21 and IL-12 inhibit differentiation of T reg and TH17 cells and enhance cytotoxicity of peripheral blood mononuclear cells in patients with cervical cancer. Int J Gynecol Cancer 21:1672–1678CrossRefPubMedGoogle Scholar
  27. 27.
    Dennis KL, Blatner NR, Gounari F, Khazaie K (2013) Currents status of IL-10 and regulatory T-cells in cancer. Curr Opin Oncol 25:637–645CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Brivio F, Fumagalli L, Parolini D et al (2008) T-helper/T-regulatory lymphocyte ratio as a new immunobiological index to quantify the anticancer immune status in cancer patients. In Vivo 22:647–650PubMedGoogle Scholar
  29. 29.
    Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 295:883–899CrossRefGoogle Scholar
  30. 30.
    Eo WK, Chang HJ, Kwon SH et al (2016) The lymphocyte-to-monocyte ratio predicts patient survival and aggressiveness of ovarian cancer. J Cancer 7:289–296CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Lewis JW, Shavit Y, Terman GV (1983) Apparent involvement of opioids peptides in stress-induced enhancement of tumor growth. Peptides 4:635–638CrossRefPubMedGoogle Scholar
  32. 32.
    Hassan ATM, Hassan ZM, Moazzeni SM (2009) Naloxone can improve the antitumor immunity by reducing the CD4+CD25+Foxp3+ regulatory T cells in BALB/c mice. Int J Immunopharmacol 9:1381–1386CrossRefGoogle Scholar
  33. 33.
    McIsaac WM (1961) Formation of 1-methyl-6-methoxy-1,2,3,4-tetrahydro-2-carboline under physiological conditions. Biochem Biophys Acta 52:607–610CrossRefGoogle Scholar
  34. 34.
    Lissoni P, Messina G, Tantarelli R et al (2017) The psychoneuroimmunotherapy of human immune-mediated systemic diseases, including cancer and autoimmune. J Mol Oncol Res 1(1):7–13Google Scholar
  35. 35.
    Lissoni P (1999) The pineal gland as central regulator of cytokine network. Neuroendocrinol Lett 20:343–349Google Scholar
  36. 36.
    Maccarone M, Valensise H, Bari M et al (2001) Progesterone up-regulates anandamide hydrolase in human lymphocytes: role of cytokines and implication in fertility. J Immunol 166:7183–7189CrossRefGoogle Scholar
  37. 37.
    Candelari PV, Rampoldi A, Harbuzariv A et al (2017) Leptin signaling and cancer chemoresistance: perspectives. Word J Clin Oncol 8:106–119CrossRefGoogle Scholar
  38. 38.
    Tesar BM, Shirali AC, Walker WE et al (2009) Aging augments IL-17 T -cell alloimmune responses. Am J Transplant 9:54–63CrossRefGoogle Scholar
  39. 39.
    Dejaco C, Duftner C, Schirmer M (2006) Are regulatory T cells linked with aging? Exp Gerontol 41:339–345CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Elenkov IJ, Papanicolaou DA, Wilder RL et al (1996) Modulatory effects of glucocorticoids and cathecolamines on human interleukin-12 and interleukin-10 production: clinical implications. Proc Assoc Am Physicians 108:374–381PubMedGoogle Scholar
  41. 41.
    Zagon IS, Donahue RN, Bonneau RH et al (2011) T lymphocyte proliferation is suppressed by the opioid growth factor met (5)-enkephalin - opioid growth factor receptor axis: implication for the treatment of autoimmune diseases. Immunobiology 216:579–590CrossRefPubMedGoogle Scholar
  42. 42.
    Aringer A, Smolen JS (2003) Complex cytokine effects in a complex autoimmune disease: tumor necrosis factor in systemic lupus erythematosus. Arthritis Res Ther 5:172–177CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Fujino S, Andoh A, Bamba S et al (2003) Increased expression of interleukin-17 in inflammatory bowel disease. Gut 52:65–70CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Arican O, Aral M, Sasmaz S et al (2005) Serum levels of TNF-alpha, IFN-gamma, IL-6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis and correlation with disease severity. Mediators Inflamm 2005(5):273–279CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Langrish CL, Chen Y, Blumenschein W et al (2005) Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med 201:233–240CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Dinarello CA (2006) Interleukin 1 and interleukin 18 as mediators of inflammation and the aging process. Am J Clin Nutr 83:447S–455SCrossRefPubMedGoogle Scholar
  47. 47.
    Lohr J, Knoechel B, Wang J et al (2006) Role of IL-17 and regulatory T lymphocytes in a systemic autoimmune disease. J Exp Med 203:2785–2791CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Paramalingam SS, Thumboo J, Vasoo S et al (2007) In vivo pro- and anti-inflammatory cytokines in normal and patients with rheumatoid arthritis. Ann Acad Med Singapore 36:96–99Google Scholar
  49. 49.
    Gold R, Luhder F (2008) Interleukin-17. Extended features of a key player in multiple sclerosis. Am J Pathol 172:8–10CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Katsifis GE, Rekka S, Moutsopoulos NM et al (2009) Systemic and local interleukin-17 and linked cytokines associated with Sjogren’s syndrome immunopathogenesis. Am J Pathol 175:1167–1177CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Murugaiyan G, Saha B (2009) Protumor vs antitumor functions of IL-17. J Immunol 183:4169–4175CrossRefPubMedGoogle Scholar
  52. 52.
    Harrison OJ, Srinivasan N, Pott J, Schiering C et al (2015) Epithelial-derived IL-18 regulates Th17 cell differentiation and Foxp3+ T reg cell function in the intestine. Mucosal Immunol 8:1226–1236CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Lee J, Shin EK, Lee SY et al (2014) Oestrogen up-regulates interleukin-21 production by CD4+ T lymphocytes in patients with systemic lupus erythematosus. Immunology 142:573–580CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Eid RE, Rao DA, Zhou J et al (1982) Interleukin-17 and interferon-gamma are produced concomitantly by human coronary artery-infiltrating T cells and act synergistically on vascular smooth muscle cells. Circulation 119:1424–1432CrossRefGoogle Scholar
  55. 55.
    Zheng C, Zhou XW, Wang JZ (2016) The dual role of cytokines in Alzheimer’s disease: update on interleukins, TNF-alpha, TGF-beta and IFN-gamma. Transl Neurodegener 5:7–18CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Ehrke MJ, Mihich E, Berd D et al (1982) Effects of anticancer drugs on the immune system in humans. Semin Oncol 16:230–239Google Scholar
  57. 57.
    Lissoni P, Brivio F, Fumagalli L et al (2009) Effects of the conventional antitumor therapies: surgery, chemotherapy, radiotherapy and immunotherapy on regulatory T lymphocytes in cancer patients. Anticancer Res 29:1847–1852PubMedGoogle Scholar

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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