title: Stage dependent destructuration of neuro-endocrine-immune system components in lung cancer patients.
abstract: BACKGROUND
  Close relationships among the nervous, endocrine and immune system components maintain body homeostasis. Alteration of time-related prophile of variation of system components and loss of integrated function may favour the developing of cancer and may be aggravated in the presence of neoplastic disease. The aim of our study was to evaluate the prophiles of time-related variation of neuro-endocrine-immune system components in lung cancer patients.
  
  
  METHODS
  Peripheral blood samples were collected at intervals of 4hours for 24hours from 11 healthy subjects (age range 35-53years, mean age±s.e. 43.6±1.7) and nine patients suffering from nonsmall cell lung cancer (age range 43-63years, mean age±s.e. 51.0±2.4). In each blood sample, lymphocyte subpopulations (CD3, CD4, CD8, HLA-DR, CD16, CD20, CD25, γδTcR) were analyzed and melatonin, cortisol, TRH, TSH, free thyroxine, GH, IGF1 and interleukin IL2 on serum were measured.
  
  
  RESULTS
  In our I-II stage lung cancer patients CD8+ lymphocytes (P=0.01), and in particular the T suppressor subset (P<0.0001), CD20+ cells (P=0.05), γδTCR expressing cells (P<0.01) and IGF1 (P=0.004) were diminished, whereas CD16+ cells (P<0.0001), CD25+ cells (P=0.03), free thyroxine (P=0.001) and GH (P<0.0001) were increased in respect of healthy subjects. In our III-IV stage lung cancer patients CD8+ lymphocytes (P=0.003) and in particular the T suppressor subset (P<0.0001), CD20+ cells (P=0.05), γδTCR expressing cells (P=0.01), melatonin (P=0.03), TSH (P=0.006) and IGF1 (P<0.0001) were diminished, whereas CD4+ cells (P=0.002), CD16+ cells (P<0.0001), CD25+ cells (P=0.002), cortisol (P=0.003), TRH (P=0.004), free thyroxine (P=0.001), GH (P<0.0001) and IL2 (P=0.0002) were increased in respect of healthy subjects. A statistically significant difference was evidenced between the two groups of cancer patients for the values of CD16+ cells (P<0.0001), free thyroxine (P=0.001) and IGF1 (P<0.0001) higher in I-II stage lung cancer patients and for the values of CD4+ cells (P<0.0001), γδTCR expressing cells (P=0.002), TRH (P=0.002) and IL2 (P=0.01) higher in III-IV stage lung cancer patients. Lung cancer patients showed alteration of the pattern of circadian variation of CD3+, CD8+, CD8+ dim, CD16+, CD20+ and γδTCR expressing cells and of cortisol, TSH and GH serum levels. Pair-wise comparisons showed severe and stage dependent alterations in lung cancer patients.
  
  
  CONCLUSIONS
  The prophiles of time-related variation of neuro-endocrine-immune system components are altered in a stage dependent manner in lung cancer patients and this alteration may impair the customary integrated system function.
authors.affiliation: Department of Internal Medicine and Chronobiology Unit, Scientific Institute and Regional General Hospital Casa Sollievo della Sofferenza, S. Giovanni Rotondo (FG), Italy. g.mazzoccoli@tin.it
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Mazzoccoli
authors.forename: Andrea
authors.initials: A
authors.lastname: Fontana
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.forename: Fabio
authors.initials: F
authors.lastname: Pellegrini
authors.forename: Ada
authors.initials: A
authors.lastname: Piepoli
authors.forename: Lucia Anna
authors.initials: LA
authors.lastname: Muscarella
authors.forename: Valerio
authors.initials: V
authors.lastname: Pazienza
authors.forename: Francesco
authors.initials: F
authors.lastname: Giuliani
authors.forename: Roberto
authors.initials: R
authors.lastname: Tarquini
mesh_terms: D000328:Adult; D018951:Antigens, CD20 / Q000032:analysis; D005260:Female; D058851:GPI-Linked Proteins / Q000032:analysis; D006801:Humans; D007107:Immune System / Q000502:physiology*; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology*; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009490:Neurosecretory Systems / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D017452:Receptors, IgG / Q000032:analysis
chemical_list: D018951:Antigens, CD20; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017452:Receptors, IgG