title: Involvement of thyroid hormones in the alterations of T-cell immunity and tumor progression induced by chronic stress.
abstract: BACKGROUND
  Stress alters the neuroendocrine system, immunity, and cancer. Although the classic stress hormones are glucocorticoids and catecholamines, thyroid hormones have also been related to stress. We recently reported that chronic restraint stress impairs T-cell mediated immunity and enhances tumor growth in mice.
  
  
  METHODS
  To study the participation of these hormones on the stress-induced alterations of the immune function and lymphoma growth, mice were subjected to acute or chronic stress, with or without thyroxin supplementation. Hormone levels, immune status, and cancer progression were evaluated.
  
  
  RESULTS
  Differential endocrine alterations were observed in response to acute and chronic stress. Although corticosterone and noradrenaline levels were increased by acute stress, they were restored after prolonged exposure to the stressor. Instead, thyroid hormone levels were only reduced in chronically stressed animals in comparison with control subjects. Correlating, chronic but not acute stress impaired T-cell reactivity. Thyroxin replacement treatment of chronic restraint stress-exposed mice, which restored the euthyroid status, reversed the observed reduction of T-cell lymphoproliferative responses. Moreover, therapeutic thyroid replacement also reversed the alterations of lymphoma growth induced by chronic stress in syngeneic mice bearing tumors as well as Interleukin-2 production and specific cytotoxic response against tumor cells. Finally, we found that the isoforms theta and alpha of the protein kinase C are involved in these events.
  
  
  CONCLUSIONS
  These results show for the first time that thyroid hormones are important neuroendocrine regulators of tumor evolution, most probably acting through the modulation of T-cell mediated immunity affected by chronic stress.
authors.affiliation: Centro de Estudios Farmacológicos y Botánicos, Consejo Nacional de Investigaciones Científicas y Técnicas, Primera Cátedra de Farmacología, Universidad de Buenos Aires, Paraguay 2155, 1121 Buenos Aires, Argentina. lfrick@fmed.uba.ar
authors.forename: Luciana Romina
authors.initials: LR
authors.lastname: Frick
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Rapanelli
authors.forename: Ursula Agnes
authors.initials: UA
authors.lastname: Bussmann
authors.forename: Alicia Juana
authors.initials: AJ
authors.lastname: Klecha
authors.forename: Maria Laura Barreiro
authors.initials: ML
authors.lastname: Arcos
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Genaro
authors.forename: Graciela Alicia
authors.initials: GA
authors.lastname: Cremaschi
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D003345:Corticosterone / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D008223:Lymphoma / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D012149:Restraint, Physical / Q000379:methods; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D013963:Thyroid Hormones / Q000008:administration & dosage / Q000378:metabolism*; D013974:Thyroxine / Q000494:pharmacology; D014316:Tritium / Q000378:metabolism
chemical_list: D008934:Mitogens; D013963:Thyroid Hormones; D014316:Tritium; D003208:Concanavalin A; D011493:Protein Kinase C; D013974:Thyroxine; D013936:Thymidine; D003345:Corticosterone; D009638:Norepinephrine