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INVESTIGATIVE
UROLOGY
Radiation
increases fibrogenic cytokine expression by Peyronie’s disease fibroblasts
Mulhall JP, Branch J, Lubrano T, Shankey TV
From the Departments of Urology, Loyola University Medical Center, Stritch
School of Medicine, Maywood, Hines Veterans Affairs Hospital and Andrology
Research Laboratory, Veterans Affairs Hospital, Hines, Illinois
J Urol. 2003; 170: 281-4
- Purpose:
Peyronie’s disease is a crippling penile deformity that
results from fibrosis in the tunica albuginea. To our knowledge its
cause is unknown and empirical therapies are used extensively. A factor
involved in the development of Peyronie’s disease is fibrogenic
cytokine over expression. Radiation therapy is an empirical therapy
for this condition and, while some data suggest a role for it, no literature
exists on the effects of radiation on tunical tissue or cells derived
from this tissue. We evaluated the effect of radiation on fibrogenic
cytokine production in cells cultured from Peyronie’s disease
plaque tissue.
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Methods and Materials:
Using a well established cell culture model cells derived from Peyronie’s
disease plaque tissue and neonatal foreskins were irradiated with 5
Gy (treatment group) or left nonirradiated (control group). At 24 hours
cells were harvested and the supernatant was analyzed using enzyme-linked
immunosorbent assay to determine the levels of the 2 fibrogenic cytokines
basic fibroblast growth factor and platelet-derived growth factor-AB.
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Results:
Four Peyronie’s disease plaque derived cultures and 2 neonatal
foreskin derived cultures were analyzed. All plaque derived fibroblasts
demonstrated significant elevations in basic fibroblast growth factor
and platelet-derived growth factor-AB compared with foreskin derived
fibroblasts.
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Conclusions:
These data suggest that radiation may in fact increase the production
of fibrogenic cytokines, which may promote the fibrotic process involved
in Peyronie’s disease. Further study is aimed at defining the
effect of irradiation on plaque tissue.
- Editorial
Comment
Repeated tunical mechanical stress and microvascular trauma is one the
most accepted causes of Peyronie’s disease. Microvascular trauma
or subtunical bleeding consequent to sexual intercourse can result in
fluid and fibrinogen in the subtunical layers. The resulting fibrin
deposits may initiate a wound healing response, which in addition to
pain and hematoma; determine a subsequent inflammatory response with
recruitment of macrophages and neutrophils. These cells release a variety
of cytokines and vasoactive factors that may lead to a fibrotic reaction
(1-4).
Among nonsurgical options for management of Peyronie’s disease,
extracorporeal shock wave therapy and radiation are proposed. Nevertheless,
there is no clear information on the effects of radiation on tissue
of Peyronie’s disease. In this elegant study, the authors used
their established cell culture model to define the effects of radiation
on the biology of Peyronie’s disease plaque tissue derived fibroblasts.
Interestingly and surprisingly, the authors found that radiation at
a dose of 5 Gy induced the Peyronie’s disease fibroblasts to dramatically
increase the production of basic fibroblast growth factor and platelet-derived
growth factor-AB, when compared to controls. These findings suggest
that radiation therapy would determine the fibrotic process of the disease,
and, therefore, worsen the Peyronie’s plaque.
References
1. Graziottin TM, Resplande J, Gholami SS, Lue TF: Peyronie’s disease.
Int Braz J Urol. 2001; 27: 326-40.
2. Somers KD, Dawson DM: Fibrin deposition in Peyronie’s disease
plaque. J Urol. 1997; 157: 311-5.
3. Diegelmann RF: Cellular and biochemical aspects of normal and abnormal
wound healing: an overview. J Urol. 1997; 157: 298-302.
4. Van de Water L: Mechanisms by which fibrin and fibronectin appear in
healing wounds: implications for Peyronie’s disease. J Urol. 1997;
157: 306-10.
Dr.
Francisco J.B. Sampaio
Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil
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