Journal Article

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

Gollnick, S O, Evans, S S, Wang, W C, Owczarczak, B, Vaughan, L, Henderson, B W, Maier, P, Baumann, H, Unger, E

2003

Overview

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 ® 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 enhanced production of chemokines, IL-6 and adhesion molecules. Subsequent studies showed that PDT-induced neutrophil recruitment is dependent upon the presence of MIP-2 and E-selectin, but not on IL-6 or KC. These results demonstrate a PDT-induced inflammatory response similar to, but less severe than obtained with Photofrin ® PDT. They also lay the mechanistic groundwork for further ongoing studies that attempt to optimise PDT through the modulation of the critical inflammatory mediators.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Animals / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Cancer Research / Cell Adhesion / Cell Movement - drug effects / Chemokine CXCL1 / Chemokine CXCL2 / Chemokines - metabolism / Chemokines - physiology / Chemokines, CXC - metabolism / Chemotactic Factors - metabolism / Chlorophyll - analogs & derivatives / Chlorophyll - therapeutic use / Cytokines - physiology / Drug Resistance / E-Selectin - metabolism / Enzyme-Linked Immunosorbent Assay / Epidemiology / Experimental Therapeutics / Female / Flow Cytometry / Fluorescent Antibody Technique / Humans / Inflammation - immunology / Intercellular Adhesion Molecule-1 - metabolism / Intercellular Signaling Peptides and Proteins - metabolism / Interleukin-6 - metabolism / Leukocytes - metabolism / Mammary Neoplasms, Experimental - drug therapy / Mammary Neoplasms, Experimental - immunology / Mammary Neoplasms, Experimental - pathology / Medical sciences / Mice / Mice, Inbred BALB C / Molecular Medicine / Monokines - metabolism / Neutrophils - physiology / Oncology / Photochemotherapy / Photoradiation therapy and photosensitizing agent / Photosensitizing Agents - therapeutic use / Treatment with physical agents / Treatment. General aspects / Tumors / Up-Regulation