Interleukin-6 trans signalling enhances photodynamic therapy by modulating cell cycling

Photodynamic therapy (PDT) of solid tumours causes tissue damage that elicits local and systemic inflammation with major involvement of interleukin-6 (IL-6). We have previously reported that PDT-treated cells lose responsiveness to IL-6 cytokines. Therefore, it is unclear whether PDT surviving tumour cells are subject to regulation by IL-6 and whether this regulation could contribute to tumour control by PDT. We demonstrate in epithelial tumour cells that while the action of IL-6 cytokines through their membrane receptors is attenuated, regulation by IL-6 via trans-signalling is established. Soluble interleukin-6 receptor-α (IL-6Rα) (sIL-6Rα) and IL-6 were released by leucocytes in the presence of conditioned medium from PDT-treated tumour cells. Cells that had lost their membrane receptor IL-6Rα due to PDT responded to treatment with the IL-6R–IL-6 complex (Hyper-IL-6) with activation of signal transducers and activator of transcription (STAT3) and ERK. Photodynamic therapy-treated cells, which were maintained during post-PDT recovery in presence of IL-6 or Hyper-IL-6, showed an enhanced suppression of proliferation. Cytokine-dependent inhibition of proliferation correlated with a decrease in cyclin E, CDK2 and Cdc25A, and enhancement of p27kip1 and hypophosphorylated Rb. The IL-6 trans-signalling-mediated attenuation of cell proliferation was also effective in vivo detectable by an improved Colon26 tumour cure by PDT combined with Hyper-IL-6 treatment. Prevention of IL-6 trans-signalling using soluble gp130 reduced curability. The data suggest that the post-PDT tumour milieu contains the necessary components to establish effective IL-6 trans-signalling, thus providing a means for more effective tumour control

Performance of the ATLAS Detector using First Collision Data

More than half a million minimum-bias events of LHC collision data were collected by the ATLAS experiment in December 2009 at centre-of-mass energies of 0.9 TeV and 2.36 TeV. This paper reports on studies of the initial performance of the ATLAS detector from these data. Comparisons between data and Monte Carlo predictions are shown for distributions of several track- and calorimeter-based quantities. The good performance of the ATLAS detector in these first data gives confidence for successful running at higher energies