Interferon gamma-producing ability in blood lymphocytes of patients with lung cancer through activation of the innate immune system by BCG cell wall skeleton

An in vitro assay system was developed to assess the potency of the human innate immune system by measurement of IL-12, IL-18, IL-10 and IFNγ in the supernatants of bacillus Calmette-Guerin cell wall skeleton (BCG-CWS)-stimulated blood samples. BCG-CWS is a ligand for Toll-like receptor (TLR) 2 and...

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Bibliographic Details
Published in:International immunopharmacology 2001-08, Vol.1 (8), p.1559-1569
Main Authors: Matsumoto, M., Seya, T., Kikkawa, S., Tsuji, S., Shida, K., Nomura, M., Kurita-Taniguchi, M., Ohigashi, H., Yokouchi, H., Takami, H., Hayashi, A., Azuma, I., Masaoka, T., Kodama, K., Toyoshima, K.
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - pharmacology
Adult
Aged
BCG Vaccine - immunology
BCG Vaccine - pharmacology
Biological and medical sciences
Cell Wall Skeleton - immunology
Cell Wall Skeleton - pharmacology
Cytokine profiles in lung cancer
Female
g-Interferon
Humans
IFNγ
IL-12 p40
IL-18
IL-23
Immune System - drug effects
Immune System - metabolism
Immunomodulators
Interferon-gamma - biosynthesis
Interferon-gamma - blood
Lung Neoplasms - blood
Lung Neoplasms - immunology
Lymphocytes - blood
Lymphocytes - drug effects
Lymphocytes - immunology
Male
Medical sciences
Middle Aged
Patients
Pharmacology. Drug treatments
Toll-like receptors
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Summary:An in vitro assay system was developed to assess the potency of the human innate immune system by measurement of IL-12, IL-18, IL-10 and IFNγ in the supernatants of bacillus Calmette-Guerin cell wall skeleton (BCG-CWS)-stimulated blood samples. BCG-CWS is a ligand for Toll-like receptor (TLR) 2 and 4, and activates monocytes to macrophages (Mφ), and immature dendritic cells to mature antigen-presenting cells (APC). This system was found to allow the discrimination of immune suppressive states in patients with lung cancer from normal immune states in light of the cytokine profile. The following results were deduced from analyses of BCG-CWS-stimulated blood samples of lung cancer patients with reference to normal subjects. (1) The levels of production of IFNγ and IL-10 by lymphocytes were decreased. (2) IL-12 p40 production by monocytes/Mφ was upregulated, while that of IL-10 was downregulated. (3) IL-18 was detected in all patients in a range similar to normal subjects. (4) Responses of lymphocytes to IL-2 and IL-18 in terms of IFNγ production were diminished. (5) The upregulated IL-12 levels were recovered to within the normal range in most patients after tumor resection. (6) Male patients showed more severe suppression of IL-12/IL-18-mediated IFNγ production than female patients. Thus, the lesser IFNγ production observed in patients' blood with high IL-12 p40 levels in response to BCG-CWS may reflect the production of p40 dimers or IL-23 instead of p70, or the presence of some unknown pathways to prohibit the interface between the innate and acquired immune systems. BCG-CWS-mediated Toll signaling may participate in IFNγ induction for lymphocytes through Mφ/APC IL-12/IL-18 modulation.
ISSN:1567-5769
1878-1705
DOI:10.1016/S1567-5769(01)00071-6