BACKGROUND: Immunotherapy of cancer by vaccination is hampered by tumour-mediated immune suppression, to which pro-inflammatory cytokines such as interleukin-1 (IL-1) and IL-6 contribute. In mouse models, IL-1-receptor antagonist (IL-1 Ra) diminished inflammation and tumour growth when administered during or shortly after tumour inoculation. MATERIALS AND METHODS: The capacity of IL-1 Ra anakinra to reduce IL-1-induced production of IL-6 in order to improve the efficacy of a subsequent booster vaccination with survivin-derived peptides and soluble β-glucan as adjuvant was tested in colon-26 adenocarcinoma-bearing Balb/c-mice. RESULTS: Bolus administration of anakinra into non-immunized mice with macroscopic tumour significantly lowered serum levels of IL-6 without inhibiting tumour growth. When administered to pre-immunized mice bearing a palpable tumour, IL-1 Ra enhanced growth inhibition of a subsequent booster vaccination, although serum-IL-6 was not reduced and the number of IFN-γ-producing splenic CD8(+) T-cells was not increased. CONCLUSION: Anakinra contributes to growth-inhibition of small tumours, presumably by blocking IL-1 as tumour growth-promoting factor rather than by facilitating an enhanced CTL response.
BACKGROUND: Immunotherapy of cancer by vaccination is hampered by tumour-mediated immune suppression, to which pro-inflammatory cytokines such as interleukin-1 (IL-1) and IL-6 contribute. In mouse models, IL-1-receptor antagonist (IL-1 Ra) diminished inflammation and tumour growth when administered during or shortly after tumour inoculation. MATERIALS AND METHODS: The capacity of IL-1 Ra anakinra to reduce IL-1-induced production of IL-6 in order to improve the efficacy of a subsequent booster vaccination with survivin-derived peptides and soluble β-glucan as adjuvant was tested in colon-26 adenocarcinoma-bearing Balb/c-mice. RESULTS: Bolus administration of anakinra into non-immunized mice with macroscopic tumour significantly lowered serum levels of IL-6 without inhibiting tumour growth. When administered to pre-immunized mice bearing a palpable tumour, IL-1 Ra enhanced growth inhibition of a subsequent booster vaccination, although serum-IL-6 was not reduced and the number of IFN-γ-producing splenic CD8(+) T-cells was not increased. CONCLUSION: Anakinra contributes to growth-inhibition of small tumours, presumably by blocking IL-1 as tumour growth-promoting factor rather than by facilitating an enhanced CTL response.
Authors: Upendra K Kar; Janina Jiang; Cheryl I Champion; Sahar Salehi; Minu Srivastava; Sherven Sharma; Shahrooz Rabizadeh; Kayvan Niazi; Valerie Kickhoefer; Leonard H Rome; Kathleen A Kelly Journal: PLoS One Date: 2012-07-11 Impact factor: 3.240