Hormone and cytokine circadian alteration in non-small cell lung cancer patients

Dept Medical Sciences, Div Internal Medicine and Chronobiology Unit, IRCCS Scientific Institute and Regional General Hospital Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy.
International journal of immunopathology and pharmacology (Impact Factor: 1.62). 07/2012; 25(3):691-702.
Source: PubMed


Alterations in hormone secretion and cytokine levels have been evidenced in many neoplastic diseases. In this study we have evaluated the circadian profile of growth hormone (GH), insulin-like growth factor-1 (IGF-1), interleukin-2 (IL2), melatonin (MEL) and cortisol (COR) serum levels in non-small cell lung cancer patients. Blood was sampled every 4 h for 24 h in 11 healthy (H) men (ages 35-53 years) and 9 men with stage 2, 3 or 4 non-small cell lung cancer (C) (ages 43-63 years). Serum GH, total IGF1, IL2, MEL and COR were measured and examined for group differences, trends, and rhythm characteristics. 24-h means were significantly higher in C234 vs H for GH, GH/IGF1, IL2 and COR, and lower for IGF1, but IL2 and COR were not different for C23 vs H. A linear regression across 4 groups (H, C2, C3, C4) found a positive trend for COR, GH, GH/IGF1 and IL2, and a negative trend for IGF1. A linear regression run between the 24-h mean levels of GH, IGF1, COR, MEL and IL2 in healthy subjects evidenced a statistically significant positive trend between MEL and GH (R=0.281, p=0.022) and in cancer patients showed a statistically significant negative trend between GH and IGF1 (R=0.332, p=0.01), COR and IGF1 (R=0.430, p=0.001), and a statistically significant positive trend between the 24-h mean of COR and GH (R=0.304, p=0.02). Rhythms in MEL and COR (peaks near 01:00h and 08:00h, respectively) indicated identical synchronization to the light-dark cycle for both groups. A circadian rhythm was detected in GH and GH/IGF1 for C23 and H, with IGF1 and IL2 non-rhythmic in any group. In conclusion, an increasing trend and progressive loss of circadian rhythmicity in GH and GH/IGF1, an increasing trend in cortisol and IL2, and a decreasing trend in IGF1 in C, reflect a complex chain of events that could be involved in progression of neoplastic disease. A therapeutic strategy needs to take into account circadian patterns and complex interactions of the multiple functions that characterize the hormone and cytokine levels in the frame cancer progression.

Download full-text


Available from: Gianluigi Mazzoccoli, May 29, 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Various features, components, and functions of the immune system present daily variations. Immunocompetent cell counts and cytokine levels present variations according to the time of day and the sleep-wake cycle. Moreover, different immune cell types, such as macrophages, natural killer cells, and lymphocytes, contain a circadian molecular clockwork. The biological clocks intrinsic to immune cells and lymphoid organs, together with inputs from the central pacemaker of the suprachiasmatic nuclei via humoral and neural pathways, regulate the function of cells of the immune system, including their response to signals and their effector functions. Consequences of this include, for example, the daily variation in the response to an immune challenge (e.g., bacterial endotoxin injection) and the circadian control of allergic reactions. The circadian-immune connection is bidirectional, because in addition to this circadian control of immune functions, immune challenges and immune mediators (e.g., cytokines) were shown to have strong effects on circadian rhythms at the molecular, cellular, and behavioral levels. This tight crosstalk between the circadian and immune systems has wide-ranging implications for disease, as shown by the higher incidence of cancer and the exacerbation of autoimmune symptoms upon circadian disruption. (Author correspondence: g.mazzoccoli@operapadrepio.it).
    Chronobiology International 05/2013; 30(7). DOI:10.3109/07420528.2013.782315 · 3.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Endocrine-immune system interactions are the basis for predominance of autoimmune diseases in women with differences between the fertile and the postmenopausal periods. B cell-driven diseases reach the maximum incidence rate in the reproductive years, at least in women under the effects of serum estrogens and their metabolites (endocrine synthesis). On the other hand, the prevalent peripheral synthesis of estrogens, especially in advanced ages (intracrine synthesis), through the action of aromatases, modulate the immune/inflammatory response in peripheral tissues similarly in both female and male patients (final common pathway). Interestingly, tissue injury that occurs during chronic immune/inflammatory reaction induces tissue repair and homeostatic responses including cell proliferation, growth factor production and angiogenesis that might facilitate cancer progression. The successful treatment of chronic immune/inflammatory diseases obtained by using medications initially developed for use in oncology, such as antiproliferative drugs, B-cell depleting monoclonal antibodies support the inflammation-cancer link.
    Expert Review of Clinical Immunology 12/2013; 10(1). DOI:10.1586/1744666X.2014.863149 · 2.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Non-small-cell lung cancer (NSCLC) is a highly prevalent and aggressive disease. In the metastatic setting, major advances include the incorporation of immunotherapy and targeted therapies into the clinician's therapeutic armamentarium. Standard chemotherapeutic regimens have long been reported to interfere with the immune response to the tumor; conversely, antitumor immunity may add to the effects of those therapies. The aim of immunotherapy is to specifically enhance the immune response directed to the tumor. Recently, many trials addressed the role of such therapies for metastatic NSCLC treatment: ipilimumab, tremelimumab, nivolumab and lambrolizumab are immunotherapeutic agents of main interest in this field. In addition, anti-tumor vaccines, such as MAGE-A3, Tecetomide, TG4010, CIMAvax, ganglioside vaccines, tumor cell vaccines and dendritic cell vaccines, emerged as potent inducers of immune response against the tumor. The current work aims to address the most recent developments regarding these innovative immunotherapies and their implementation in the treatment of metastatic NSCLC.
    Immunotherapy 11/2014; 6(11):1221-35. DOI:10.2217/imt.14.82 · 2.07 Impact Factor
Show more