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Clinical Studies |
Medizinische Klinik (L.C.H., A.K., A.E.H.) and Augenklinik (H.D.S.), Klinikum Innenstadt, Ludwig-Maximilians-Universität, Munich; Städtisches Klinikum-West (T.M.), Leipzig; and Augenpraxis Prof. Neuhann (G.H.), Munich, Germany
Address all correspondence and requests for reprints to: Armin E. Heufelder, Division of Endocrinology, Medizinische Klinik, Klinikum Innenstadt, Ludwig-Maximilians-Universität, Ziemssenstraße 1 80336 Munich Germany.
Interleukin-1 (IL-1) plays an important role in the pathogenesis of
Graves’ ophthalmopathy (GO). Impaired antagonism of the
proinflammatory cytokine IL-1 by the naturally occurring IL-1 receptor
antagonist (IL-1RA) has been implicated in the initiation and
perpetuation of various autoimmune diseases and may play a role in the
evolution of GO. Cigarette smoking appears to adversely affect the
course of GO. We have evaluated the course of IL-1
, IL-1ß, and
soluble IL-1RA (sIL-1RA) serum levels in smokers and nonsmokers with GO
undergoing orbital radiotherapy (OR). We prospectively studied the eye
status of 27 randomly selected patients (mean age 47.3 ± 11.0 yr;
20 females; 18 smokers) with active, moderately severe GO before and 3
and 6 months following OR, respectively. None had received any previous
treatment for GO, and all patients were kept euthyroid on carbimazole.
Serum concentrations of IL-1, IL-1ß, and sIL-1RA were measured
using highly sensitive enzyme linked immunosorbent assay systems.
Baseline sIL-1RA levels were negatively correlated with the number of
cigarettes smoked before and following OR (P <
0.0001). Patients with no or minor therapeutic response to OR (n =
8), all of whom were smokers, revealed mean baseline sIL-1RA levels of
114 ± 85 pg/mL, which increased to 172 ± 103 pg/mL at 3
months and 149 ± 96 pg/mL at 6 months after initiation of OR,
respectively. By contrast, patients with a good clinical response
(n = 19, 9 nonsmokers), revealed significantly higher baseline
sIL-1RA levels at 294 ± 148 pg/mL (P =
0.004), which increased to 845 ± 668 pg/mL at 3 months
(P = 0.01) and 634 ± 337 pg/mL at 6 months
(P < 0.001), respectively, following initiation of
OR. Serum concentrations of IL-1 and IL-1ß were below 3.9 pg/mL in
all patients with GO who were studied, and were not correlated with
gender, age, smoking status, clinical course, or outcome. Low baseline
levels and impaired surge of sIL-1RA serum levels following OR were
strongly correlated with smoking status and a less favorable
therapeutic outcome in patients with active, moderately severe GO.
Measurement of sIL-1RA may contribute to predict the therapeutic
response to OR in patients with active, moderately severe GO.
Strategies designed to raise local or systemic concentrations of
sIL-1RA may be of benefit to patients with GO.
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