Original articles

Cancer Immunology, Immunotherapy

, Volume 34, Issue 5, pp 306-312

First online:

Induction of urinary interleukin-1 (IL-1), IL-2, IL-6, and tumour necrosis factor during intravesical immunotherapy with bacillus Calmette-Guérin in superficial bladder cancer

  • E. C. De BoerAffiliated withLaboratory for Pathology, National Institute of Public Health and Environmental Protection (RIVM)
  • , W. H. De JongAffiliated withLaboratory for Pathology, National Institute of Public Health and Environmental Protection (RIVM)
  • , P. A. SteerenbergAffiliated withLaboratory for Pathology, National Institute of Public Health and Environmental Protection (RIVM)
  • , L. A. AardenAffiliated withCentral Laboratory of the Netherlands Red Cross Blood Transfusion Service
  • , E. TetterooAffiliated withLaboratory for Pathology, National Institute of Public Health and Environmental Protection (RIVM)
  • , E. R. De GrootAffiliated withCentral Laboratory of the Netherlands Red Cross Blood Transfusion Service
  • , A. P. M. Van der MeijdenAffiliated withDepartment of Urology, University Hospital NijmegenDepartment of Urology, Grootziekengasthuis, 's-Hertogenbosch
  • , P. D. J. VegtAffiliated withDepartment of Urology, St. Elisabeth Hospital
  • , F. M. J. DebruyneAffiliated withDepartment of Urology, University Hospital Nijmegen
    • , E. J. RuitenbergAffiliated withCentral Laboratory of the Netherlands Red Cross Blood Transfusion ServiceInstitute of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, State University Utrecht

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Summary

To study the local immunological effects of intravesical bacillus Calmette-Guérin (BCG) therapy in superficial bladder cancer patients, the production of interleukin-1 (IL-1), IL-2, IL-6, tumour necrosis factor α (TNFα), and interferon γ (IFNγ) was investigated in the urine. Urine specimens were collected during the six weekly BCG instillations, before instillation, and 2, 4, 6, 8, and 24 h thereafter. Results were standardized to urine creatinine. In general, the concentration of IL-1 increased markedly during the first three BCG instillations, reaching a plateau from instillations 3 to 6. IL-2 was not detected after the first BCG instillation, but from the second instillation onwards the mean IL-2 concentration increased rapidly. With respect to IL-6, patients had relatively high levels in the urine after the first BCG instillation. A relatively moderate increase of the IL-6 concentration was observed during the following weeks. Like IL-2, TNFα was only detected after repeated BCG instillations. Generally the highest TNF levels were found after BCG instillation 5. The presence of IFNγ could not be demonstrated. With respect to the occurrence of the cytokines during the first 24 h after the BCG instillation, TNF, IL-2, and IL-6 were detectable 2 h after the instillation. In contrast, IL-1 seemed to appear later, i.e. from 4 h onwards. TNF decreased most rapidly; it was nearly absent in 6-h samples. Generally IL-2 was not detectable in the 8-h samples, whereas IL-1 and IL-6 were present up to 8 h after instillation of BCG. The presence of TNF was found less frequently than the presence of IL-1, IL-2, and IL-6. Neutralization experiments indicated that most of the IL-1 present in the urine after BCG treatment was IL-1α. In conclusion, activation of BCG-specific T cells was indicated by the detection of IL-2. The presence of IL-1, IL-6, and TNFα might suggest activation of macrophages by intravesically administered BCG, although production by other cell types cannot be excluded. It is suggested that these cytokines, in combination with the leucocytes that are known to be recruited to the bladder in reaction to the BCG treatment, may play an important role in the antitumour activity of BCG against bladder cancer. For monitoring purposes, collection of urine might be performed during the first 6 h after BCG instillations 4–6. A correlation between the presence of cytokines in the urine and the clinical response has yet to be evaluated.

Key words

BCG vaccine Immunotherapy Bladder neoplasms Interleukin-1 Interleukin-2 Interleukin-6 Tumour necrosis factor