title: IL-6 potentiates tumor resistance to photodynamic therapy (PDT).
abstract: OBJECTIVE
  Photodynamic therapy (PDT) is an anticancer modality approved for the treatment of early disease and palliation of late stage disease. PDT of tumors results in the generation of an acute inflammatory response. The extent and duration of the inflammatory response is dependent upon the PDT regimen employed and is characterized by rapid induction of proinflammatory cytokines, such as IL-6, and activation and mobilization of innate immune cells. The importance of innate immune cells in long-term PDT control of tumor growth has been well defined. In contrast the role of IL-6 in long-term tumor control by PDT is unclear. Previous studies have shown that IL-6 can diminish or have no effect on PDT antitumor efficacy.
  
  
  METHODS
  In the current study we used mice deficient for IL-6, Il6(-/-) , to examine the role of IL-6 in activation of antitumor immunity and PDT efficacy by PDT regimens known to enhance antitumor immunity.
  
  
  RESULTS
  Our studies have shown that elimination of IL-6 had no effect on innate cell mobilization into the treated tumor bed or tumor draining lymph node (TDLN) and did not affect primary antitumor T-cell activation by PDT. However, IL-6 does appear to negatively regulate the generation of antitumor immune memory and PDT efficacy against murine colon and mammary carcinoma models. The inhibition of PDT efficacy by IL-6 appears also to be related to regulation of Bax protein expression. Increased apoptosis was observed following treatment of tumors in Il6(-/-) mice 24 hours following PDT.
  
  
  CONCLUSIONS
  The development of PDT regimens that enhance antitumor immunity has led to proposals for the use of PDT as an adjuvant treatment. However, our results show that the potential for PDT induced expression of IL-6 to enhance tumor survival following PDT must be considered.
authors: Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors: Craig M
authors: CM
authors: Brackett
authors: Barbara
authors: B
authors: Owczarczak
authors: Kimberley
authors: K
authors: Ramsey
authors: Patricia G
authors: PG
authors: Maier
authors: Sandra O
authors: SO
authors: Gollnick
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002734:Chlorophyll / Q000031:analogs & derivatives / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000276:immunology; D017323:Dihematoporphyrin Ether / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000276:immunology*; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D015850:Interleukin-6; D017319:Photosensitizing Agents; D051028:bcl-2-Associated X Protein; D002734:Chlorophyll; C083998:2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a; D017323:Dihematoporphyrin Ether