The immune system during the pre‐cancer and the early cancer period. IL‐2 production by PBL from post‐menopausal women with and without endometrial carcinoma

Yron, Ilana; Schickler, Michael; Fisch, B.; Pinkas, Haim; Ovadia, Jardena; Witz, Isaac P.

doi:10.1002/ijc.2910380306

Cited by 20 publications

(7 citation statements)

References 38 publications

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“…A lower production of IFN-Á and IL-2 by PBMC of cancer patients has already been reported by other authors [19][20][21][22] and we could show in several earlier studies that an impaired IFN-Á production becomes more apparent as the tumor load increases [16,23]. However, in all those studies only Th1 cytokines were measured.…”

Section: Discussioncontrasting

confidence: 38%

Th1 and Th2 Cytokine Response Patterns in Leukocyte Cultures of Patients with Urinary Bladder, Renal Cell and Prostate Carcinomas

Elsässer‐Beile

Kölble²,

Grussenmeyer³

et al. 1998

Tumor Biol

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As a decreased production of Th1 cytokines by stimulated peripheral blood leukocytes has recently been shown in patients with various carcinomas, the present study was performed to determine whether these patients also exhibit a Th1/Th2 imbalance compared to healthy controls. We measured the production of the Th1 cytokines IL-2 and IFN-γ as well as the Th2 cytokines IL-4, IL-6 and IL-10 in mitogen-stimulated peripheral blood mononuclear cell (PBMC) cultures of patients with urinary bladder carcinomas (n = 47), prostate carcinomas (n = 111) and renal cell carcinomas (n = 67) as compared to 40 age-matched healthy controls. In the PBMC cultures of the tumor patients, the levels of the Th1 cytokines IL-2 and IFN-γ were lower as compared to the controls. For IFN-γ, the differences were highly significant and in the patients with renal cell carcinomas it could be shown that the values decreased with increasing tumor mass. In contrast, the levels of the Th2 cytokines IL-4, IL-6 and IL-10 were comparable in the PBMC cultures of tumor patients and controls. From these results, it is concluded that there is only a malfunction in Th1 cells but no switch from a Th1 type to a Th2 type cytokine profile in the PBMCs of cancer patients.

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Section: Discussioncontrasting

confidence: 38%

Th1 and Th2 Cytokine Response Patterns in Leukocyte Cultures of Patients with Urinary Bladder, Renal Cell and Prostate Carcinomas

Elsässer‐Beile

Kölble²,

Grussenmeyer³

et al. 1998

Tumor Biol

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“…In one study, an impaired production of TNF was found (Zielinski et al, 1990) and a defective expression and release of the IL-2 receptors (Hakim, 1988), while in another study the production of IL-2 was not diminished (Wanebo et al, 1986). In lymphocyte cultures of patients with endometrial carcinomas a reduced IL-2 production has been described (Yron et al, 1986).…”

Section: Discussionmentioning

confidence: 97%

Impaired cytokine production in whole blood cell cultures of patients with gynaecological carcinomas in different clinical stages

Elsässer‐Beile

Kleist²,

Sauther³

et al. 1993

Br J Cancer

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Summary The production of the cytokines IFN-gamma, IL-1-alpha, IL-2 and TNF-alpha was investigated in mitogen-stimulated, whole blood cell culturs from 239 untreated patients with primary gynaecological carcinomas (breast, cervix, ovary, endometrium), and 191 healthy female controls.The cytokines were measured in the 4-day post-inductional supernatants by a sensitive enzymoimmunological assay. In the blood cell cultures of all four groups of cancer patients, significantly lower values of IFN-gamma (P < 0.001), IL-2 (P < 0.01) and IL-1 alpha (P < 0.01) were found as compared to the controls, although lymphocyte and monocyte counts were almost identical.Grouping the tumour patients into different clinical stages we could show in the four groups of carcinomas a gradual depression of the cytokine production according to growing tumour burden.The host's response to malignant tumours is usually considered to be primarily a function of the cellular immune system and various tests have been established to measure the integrity of this system in cancer patients, such as hypersensitivity skin tests (Bolton et al., 1975;Evans et al., 1977), or determination of mitogen-induced lymphocyte proliferation in vitro (Dean et al., 1977;Zembala et al., 1977;Fritze & Dystant, 1984).As the cell-mediated immune response is controlled by a series of soluble cytokines, in recent years the measurement of these substances has also been used to determine the cellular immunological potency of tumour patients (Rey et al., 1983;Santos et al., 1985;Elsasser-Beile et al., 1991a Blood samples Ten ml of heparinised blood was taken from each patient and control person between 9 and 11 a.m. The samples, kept at room temperature, were used within 2 h. A 0.5 ml aliquot was removed for total and differential leukocyte counts.Whole blood cell culture (WBCC) Cultures were performed as previously described with a system for which optimal conditions and kinetics of cytokine production were established (Elsasser-Beile et al., 1991b).In brief, heparinised venous blood was diluted 1/10 with RPMI 1640 (Seromed, Berlin FRG), which was supplemented with 50 U ml-' Penicillin (Seromed) and 50 Sg ml-' Streptomycin (Seromed) and distributed in 0.5 ml aliquots in 12 mm polystyrol tubes. For stimulation, 10 ig ml-' phytohaemagglutinin (PHA Wellcome, Burgwedel, FRG) and 0.5-5 g.g ml-' Pokeweed mitogen (PWM, Sigma, Deisenhofen, FRG) were added.Incubation of the cell cultures was performed at 37°C in a humidified atmosphere of 5% CO2. After 4 days of culture without changes of medium 320 ftl of supernatant was removed from each tube to be assayed for cytokine levels.Determination of cytokines Enzyme-linked immunoassays (ELISA) were applied for qualitative and quantitative determinations of cytokines.These tests are based on the sandwich principle and are performed in one step. Since a correlation was found between assay performance of the naturally occurring cytokines and their recombinant counterparts, the latter were used as standards.Interferon-gamma-ELISA IFN-gamma ...

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“…With IL-4, some antitumor effects were first observed in the mouse, the mechanism probably being macrophage activation [176]; these findings have encouraged the first clini cal trials [277],…”

Section: Il-4mentioning

confidence: 99%

“…Reduced IL-2 production by PBMCs seems to be one of the most frequent immune dysfunctions in patients with neoplasms, such as tumors of the gastrointestinal tract [171 -173], urinary bladder [174,175], and endo metrium [176], malignant melanomas [177], and Hodgkin's disease [178],…”

Section: Il-2 and The Il-2 Receptormentioning

confidence: 99%

Cytokines as Therapeutic and Diagnostic Agents

Elsässer‐Beile¹,

Kleist²

1993

Tumor Biol

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Cytokines are key mediators of immunity and inflammation. These proteins or glycoproteins act as communication signals between different populations of leukocytes but neither their effects nor their production are restricted to immune cells. In the last few years many new cytokines and their effects have been discovered and it was agreed that when the amino acid sequence of a new cytokine was established it would be assigned the name interleukin (IL), with an added number. The detection of cytokines in disease states promises to provide useful information for diagnostic purposes. The therapeutic utility of cytokines has been explored in many clinical and preclinical studies and in a wide variety of infectious diseases, autoimmune diseases and neoplasias. Since the production of cytokines is modulated by several biological agents such as hormones, prostaglandins and drugs, these may also serve as therapeutic targets for immunomodulation.

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The immune system during the pre‐cancer and the early cancer period. IL‐2 production by PBL from post‐menopausal women with and without endometrial carcinoma

Cited by 20 publications

References 38 publications

Th1 and Th2 Cytokine Response Patterns in Leukocyte Cultures of Patients with Urinary Bladder, Renal Cell and Prostate Carcinomas

Th1 and Th2 Cytokine Response Patterns in Leukocyte Cultures of Patients with Urinary Bladder, Renal Cell and Prostate Carcinomas

Impaired cytokine production in whole blood cell cultures of patients with gynaecological carcinomas in different clinical stages

Cytokines as Therapeutic and Diagnostic Agents

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