Induction of tumour necrosis factor-alpha (TNF-α) mRNA in bladders and spleens of mice after intravesical administration of bacillus Calmette-Guérin

Abstract

SUMMARYIntravesical bacillus Calmette-Guerin (BCG) therapy is highly eflfective in the therapy of carcinoma in situ of the bladder, but the mechanism of BCG immunotherapy is not clearly understood. We studied the production of TNF-n in spleens and bladders ofmice after intravesical BCG or BCG/interferon-gamma (iFN--}) instillation. Significant change of TNF-a mRNA expression of spleens and bladders of C3H/He mice was observed after intravesical BCG instillation, although intravesical IFN-7 therapy 3 days after BCG instillation to maintain the activated state of monocyte/macrophage lineage cells did not show a significant change of TNF-a mRNA, compared with that of BCG therapy alone. Maximal production of TNF-a mRNA in spleens of mice was seen after the first or second intravesical BCG instillation, and production of TNF-fi mRNA in bladders was also increased after intravesical BCG instillation. The increment of TNF-rt production by BCG stimulation in HL-60. a promyelocytic leukaemic cell line, and peripheral blood mononuclear cells in vitro may support Ihe in vivo effect of BCG therapy on the bladder. These data show that local production of TNF-a as well as systemic production by intravesical BCG treatment may correlate with one of the mechanisms of BCG immunotherapy of superficial bladder cancer.

Mycobacterium bovis BCG promotes tumor cell survival from tumor necrosis factor-α-induced apoptosis

“…While absence of p53 can be attributed to the reduced TNF-α responses and diminished p53 functions in HCT116 p53 -/- cells, the possible reasons for the observations in MDA-MB-231 with mutant p53 is currently under investigation. Further, though BCG treatment, by itself, can induce the expression of TNF-α in immune cells [ 23 ] and during BCG therapy [ 49 ], in the current study we addressed the ability of BCG to revert the TNF-α responses such as apoptosis during therapy. However, BCG failed to protect A549 cells against apoptosis induced by other death ligands of the TNF family such as TRAIL (Additional file 2 : Figure S2).…”

Should intravesical Bacillus Calmette-Guérin be employed in transplant recipients with bladder carcinoma?

“…IL‐2, IFN‐γ, and TNF are potent pro‐inflammatory cytokines that are associated with antigen recognition. Animal and in vitro model investigations have demonstrated that effective immunotherapy with BCG involves a shift of cytokine responses toward Th1 (19–22). Furthermore, this immune activation may be persistent.…”

Wirkmechanismen der intravesikalen BCG-Immuntherapie des oberflächlichen Harnblasenkarzinoms

“…Die BCGBehandlung führt zur vermehrten IFN-γ-Expression und zur Herunterregulation von IL-4, was die Induktion eines T H 1-Zytokin-Profils, ähnlich der Situation im Menschen, nahe legt [36]. In einem vergleichbaren Modell induzierte BCG zusätzlich die Expression von TNF-α [56]. …”