This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by de Vree, W. J. A. Articles by Sluiter, W. Search for Related Content PubMed PubMed Citation Articles by de Vree, W. J. A. Articles by Sluiter, W.

Role of Interleukin 1 and Granulocyte Colony-Stimulating Factor in Photofrin-based Photodynamic Therapy of Rat Rhabdomyosarcoma Tumors¹

Department of Biochemistry, Erasmus University, P. O. Box 1738, 3000 DR Rotterdam, the Netherlands

Neutrophils play an important role in the efficacy of photodynamic therapy (PDT). These leukocytes rapidly accumulate into the tumor lesion after PDT and most likely eradicate the remaining attenuated tumor cells. The underlying mechanism of the accumulation of neutrophils at the time of PDT is not known. Therefore, we determined the effect of PDT on the course of mature and immature neutrophils in the circulation of rhabdomyosarcoma-bearing rats and studied the changes in the level of interleukin (IL)-1ß as an important stimulator of the proliferation of precursor cells of the granulocyte lineage in the bone marrow.

We found that the effect of PDT on tumor growth was preceded by a rapid and specific increase of the number of mature neutrophils in the peripheral blood as early as 4 h after the start of PDT treatment and reaching maximum values after 8 h. At 24 h, the neutrophil numbers in the PDT-treated rats were still elevated as compared to sham-treated rats. In sham-treated rats, the numbers of blood monocytes and lymphocytes decreased by about 50% after 2 h and returned to their normal levels as soon as 2 h later. In PDT-treated rats, the course of monocyte numbers showed a similar pattern; however, lymphocyte numbers did not reach the normal range until 24 h.

The specific increment of neutrophils was preceded by an increase of band neutrophil numbers and elevated serum levels of IL-1ß which were maximal at 2 h after the start of PDT. Pearson correlation analysis showed a significant association between the serum levels of IL-1ß at this time point and the number of band neutrophils at 4 h (R² = 0.58; P = 0.03) and the number of mature neutrophils at 8 h (R² = 0.54; P = 0.04). This suggests that PDT evoked an IL-1-dependent increased production rate of neutrophils in the bone marrow. Further investigation showed that the injection of anti-granulocyte colony-stimulating factor (G-CSF) antibodies not only attenuated the increase in neutrophil numbers but also greatly decreased the efficacy of PDT. On this basis, we suppose that an IL-1-induced release of G-CSF by PDT underlies this nonspecific immune reaction to the tumor. Apparently, G-CSF not only stimulates the production rate of neutrophils in the bone marrow but also increases the functional activity of these leukocytes to become indispensable tumor cell killers.

¹ This investigation was supported by the Dutch Cancer Society Grants EUR 91-01 and 95-1026 and a donation from Mrs. E. C. Bakker-Grieszmayer.

² To whom requests for reprints should be addressed.

Received 4/ 2/97. Accepted 5/15/97.

This article has been cited by other articles:

				E.-S. Abdel-Hady, P. Martin-Hirsch, M. Duggan-Keen, P. L. Stern, J. V. Moore, G. Corbitt, H. C. Kitchener, and I. N. Hampson Immunological and Viral Factors Associated with the Response of Vulval Intraepithelial Neoplasia to Photodynamic Therapy Cancer Res., January 1, 2001; 61(1): 192 - 196. [Abstract] [Full Text]

				M. Korbelik and G. J. Dougherty Photodynamic Therapy-mediated Immune Response against Subcutaneous Mouse Tumors Cancer Res., April 1, 1999; 59(8): 1941 - 1946. [Abstract] [Full Text] [PDF]