Urinary Cytokines During Intravesical Bacillus Calmetteguerin Therapy for Superficial Bladder Cancer: Processing, Stability and Prognostic Value

Reijke, Theo M. de; Boer, Elizabeth C. de; Kurth, K. H.; Schamhart, D. H. J.

doi:10.1016/s0022-5347(01)66424-3

Cited by 159 publications

(89 citation statements)

References 26 publications

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“…This is evident from the production of both IL-12 (Th1) and IL-10 (Th2) cytokines. In clinical practice, a burst of urinary Th1 cytokines IFNg, IL-12 and IL-2 has been observed after BCG therapy and is a common feature in BCG responders, whereas higher levels of the Th2 cytokines IL-10 and/or IL-6 appear to be associated with BCG failure de Reijke et al, 1996). Patients who failed BCG immunotherapy also showed higher antibody responses to BCG heat shock proteins in their sera (Zlotta et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Polarisation of a T-helper cell immune response by activation of dendritic cells with CpG-containing oligonucleotides: a potential therapeutic regime for bladder cancer immunotherapy

et al. 2003

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Intravesical bacillus Calmette -Guerin (BCG) is a treatment for transitional cell carcinoma (TCC) and carcinoma in situ (cis) of the urinary bladder, but some patients remain refractory. The mechanism of cancer clearance is not known, but T cells are thought to play a contributory role. Tissue dendritic cells (DCs) are known to initiate antigen-specific immune responses following activation of receptors, which recognise molecular patterns on the surface of microorganisms. A family of these receptors, the toll-like receptors (TLRs), are also crucial for activating DC to produce cytokines that polarise the T-cell response towards a T helper (Th)1 or Th2 phenotype. This study compared the potential of intact BCG to activate DC with that of the defined TLR4 ligand lipopolysaccharide (LPS) and the TLR9 ligand CpG-oligonucleotide. It was found that all three stimuli efficiently activated normal DC, but cells expressing a mutant TLR4 responded poorly to stimulation with LPS. Importantly, stimulation with BCG induced both IL-12 and IL-10, suggesting subsequent development of a poorly focused T-cell immune response containing both Th1 and Th2 immune function. By contrast, LPS-and CpG-oligonucleotides induced only IL-12, indicating the potential to produce a Th1 response, which is likely to clear cancer most efficiently. Given the toxicity of LPS, our data suggest that CpG-oligonucleotides may be beneficial for intravesical therapy of bladder cancer.

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Section: Discussionmentioning

confidence: 99%

Polarisation of a T-helper cell immune response by activation of dendritic cells with CpG-containing oligonucleotides: a potential therapeutic regime for bladder cancer immunotherapy

et al. 2003

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“…However, De Reijke et al have recently shown that decreased IL-2 production in the urine after BCG intravesical therapy (indicator of a Th1 pattern of response) had a potential as a prognostic factor of early recurrence [37].…”

Section: Discussionmentioning

confidence: 99%

Humoral response against heat shock proteins and other mycobacterial antigens after intravesical treatment with bacille Calmette–Guérin (BCG) in patients with superficial bladder cancer

Zlotta

Drowart

Huygen

et al. 1997

Clinical and Experimental Immunology

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SUMMARYFew studies have analysed the antibody response during intravesical BCG immunotherapy for superficial bladder cancer. We have examined the evolution in serum antibody response against several heat shock proteins (hsp), including the recombinant mycobacterial hsp65 and the native protein P64 from BCG, GroEL from Escherichia coli (hsp60 family), recombinant mycobacterial hsp70 and the E. coli DnaK (hsp70 family), against purified protein derivative of tuberculin (PPD) and the AG85 complex of Mycobacterium bovis BCG, as well as against tetanus toxoid in 42 patients with a superficial bladder tumour, 28 treated with six intravesical BCG instillations and 14 patients used as controls. We also analysed the lymphoproliferative response of peripheral blood mononuclear cells against PPD in this population. Data of antibody responses at 6 weeks post BCG were available in all 28 patients,

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“…IL-8 was measured in 4 times diluted urine samples using a commercially available IL-8 enzyme-linked immunosorbent assay (ELISA) [Central Laboratory of the Red Cross Blood Transfusion Services (CLB), Amsterdam, The Netherlands]. Cytokines IL-6 and IL-2 in urine were determined as reported previously [9] with commercially available ELISAs (Medgenix, Fleurus, Belgium). Patients with a positive immune response to BCG were defined as having positive urinary IL-2 and IL-6 levels, i.e., > 0.34 U IL-2/gmol creatinine and > 50.1 pg IL-6/~tmol creatinine, respectively [9].…”

Section: Urine Collection and Cytokine Measurementmentioning

confidence: 99%

“…Cytokines IL-6 and IL-2 in urine were determined as reported previously [9] with commercially available ELISAs (Medgenix, Fleurus, Belgium). Patients with a positive immune response to BCG were defined as having positive urinary IL-2 and IL-6 levels, i.e., > 0.34 U IL-2/gmol creatinine and > 50.1 pg IL-6/~tmol creatinine, respectively [9]. Cytokine data were standardized to urine creatinine [9].…”

Section: Urine Collection and Cytokine Measurementmentioning

confidence: 99%

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Role of interleukin-8 in onset of the immune response in intravesical BCG therapy for superficial bladder cancer

et al. 1997

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Role of interleukin-8 in onset of the immune response in intravesical BCG General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Abstract In intravesical therapy for superficial bladder carcinoma urothelial cells may, through the production of cytokines, contribute to the bacillus Calmette-Gu~rin (BCG)-induced local immunological reaction and associated antitumor efficacy. The aim of this study was to investigate such a role for the neutrophil-attracting cytokine interleukin-8 (IL-8). The appearance of IL-8 in patients' urine after BCG therapy was compared with BCG-induced IL-6 and IL-2 and the stability of IL-8 in urine was tested. Compared to IL-6 and IL-2, a rapid induction of IL-8 was observed, occurring after the first BCG instillation. Urinary IL-8 was highly stable, even after 24 h incubation at 37°C. The IL-8 concentration after the first instillation seemed to be associated with subsequent development of an immune response. Consequently, IL-8 seems an attractive candidate for investigation of its prognostic value for a clinical response to BCG therapy.

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Urinary Cytokines During Intravesical Bacillus Calmetteguerin Therapy for Superficial Bladder Cancer: Processing, Stability and Prognostic Value

Cited by 159 publications

References 26 publications

Polarisation of a T-helper cell immune response by activation of dendritic cells with CpG-containing oligonucleotides: a potential therapeutic regime for bladder cancer immunotherapy

Polarisation of a T-helper cell immune response by activation of dendritic cells with CpG-containing oligonucleotides: a potential therapeutic regime for bladder cancer immunotherapy

Humoral response against heat shock proteins and other mycobacterial antigens after intravesical treatment with bacille Calmette–Guérin (BCG) in patients with superficial bladder cancer

Role of interleukin-8 in onset of the immune response in intravesical BCG therapy for superficial bladder cancer

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