Role of cytokines in photodynamic therapy-induced local and systemic inflammation

作者：Sandra O. Gollnick, Sharon S. Evans, Heinz Baumann, Barbara Owczarczak, Patricia Maier, Lurine A. Vaughan, W. C. Wang, Emily Unger, Barbara W. Henderson · 发表于：British Journal of Cancer · 年份：2003 · DOI：10.1038/sj.bjc.6600864 · 被引用次数：344 · 研究领域：Photodynamic Therapy Research Studies、Nanoplatforms for cancer theranostics、Angiogenesis and VEGF in Cancer

Photodynamic therapy (PDT) of tumour results in the rapid induction of an inflammatory response that is considered important for the activation of antitumour immunity, but may be detrimental if excessive. The response is characterised by the infiltration of leucocytes, predominantly neutrophils, into the treated tumour. Several preclinical studies have suggested that suppression of long-term tumour growth following PDT using Photofrin((R)) is dependent upon the presence of neutrophils. The inflammatory pathways leading to the PDT-induced neutrophil migration into the treated tumour are unknown. In the following study, we examined, in mice, the ability of PDT using the second-generation photosensitiser 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) to induce proinflammatory cytokines and chemokines, as well as adhesion molecules, known to be involved in neutrophil migration. We also examined the role that these mediators play in PDT-induced neutrophil migration. Our studies show that HPPH-PDT induced neutrophil migration into the treated tumour, which was associated with a transient, local increase in the expression of the chemokines macrophage inflammatory protein (MIP)-2 and KC. A similar increase was detected in functional expression of adhesion molecules, that is, E-selectin and intracellular adhesion molecule (ICAM)-1, and both local and systemic expression of interleukin (IL)-6 was detected. The kinetics of neutrophil immigration mirrored those observed for the ...