Benvenuti ad Adobe GoLive 6

Cytokines, cytokine antagonists and soluble adhesion molecules in patients with ocular Behçet’s disease treated with human recombinant interferon-a2a. Results of an open study and review of the literature

I. Kötter¹, S. Koch¹, R. Vonthein², U. Rückwaldt¹, M. Amberger¹, I. Günaydin¹, M. Zierhut³, N. Stübiger³

¹University Hospital, Department of Internal Medicine II (Haematology, Oncology, Immunology and Rheumatology), Tübingen; ²Department of Medical Biometry, University of Tübingen; ³University Hos-pital, Department of Ophthalmology II, Tübingen, Germany.

ABSTRACT
Objective
To elucidate the influence that interferon-a exerts on the cytokine network in active ocular Behçet’s disease (BD).

Methods
Fifty patients with active ocular BD were treated with human recombinant interferon-a2a (rhIFN-a2a). Serum was analysed for the presence of IL-10, TNF-a, IL-8, IL-6, sIL-2R, IFN-g, IFN-a, IL-12, IL-4, sTNFRI (p55), sTNFRII (p75), IL-1RA, G-CSF, sE-selectin, sVCAM-1, sICAM-1 and neopterin before initiation of and at several time points during IFN treatment and compared to 21 healthy controls.

Results
The levels of IFN-a, IL1-RA and sTNFRII were significantly increased in the patients at baseline in comparison to healthy controls. During treatment with rhIFN-a2a, when remission was achieved as defined by the scoring system used, a significant increase in levels of IFN-a, IL-2R, TNF-a, sTNF-RII, sICAM-1, sVCAM-1, neopterin in the serum was observed, with a tendency towards increased IL-1RA as well. In contrast, leuko- and thrombocyte counts and sE-selectin serum levels significantly decreased. Positive correlations were found between IFN dosage or serum levels and sVCAM-I, neopterin, sTNF-RII and sIL-2R, between sVCAM-I, sIL-2R, TNFa, sTNF-RII and neopterin, sICAM-I and sVCAM-I, sIL2-R and sTNF-RII, and, finally, between sIL2-R and sICAM-I.

Conclusions
IFN-a exerts diverse influences mainly on cytokine antagonists and soluble adhesion molecules. Because sTNF-RII and IL-1RA were increased by IFN-a treatment, these might be interesting alternative treatment options in refractory BD. Some of the side-effects of IFN-a may be caused by activation of monocytes, which is reflected by an increase in neopterin serum levels.

Key words
Behçet’s disease, interferon-a, treatment, cytokines, cytokine antagonists soluble adhesion molecules, neopterin.

Please address correspondence to: Ina Kötter, MD, Department of Internal Medicine II, (Hematology/Oncology/Immunology/Rheumatology) University Hospital, Otfried-Müller Str. 10, D-72076 Tübingen, Germany.
E-mail: ina.koetter@med.uni-tuebingen.de