Cytokines, cytokine antagonists and soluble adhesion molecules in patients with ocular Behçet's disease treated with human recombinant interferon-alpha2a. Results of an open study and review of the literature.
OBJECTIVE
To elucidate the influence that interferon-alpha 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-alpha2a (rhIFN-alpha2a). Serum was analysed for the presence of IL-10, TNF-alpha, IL-8, IL-6, sIL-2R, IFN-gamma, IFN-alpha, 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-alpha IL1-RA and sTNFRII were significantly increased in the patients at baseline in comparison to healthy controls. During treatment with rhIFN-alpha2a, when remission was achieved as defined by the scoring system used, a significant increase in levels of IFN-alpha, IL-2R, TNF-alpha, 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-1, sIL-2R, TNF-alpha, sTNF-RII and neopterin, sICAM-I and sVCAM-1, sIL2-R and sTNF-RII, and, finally, between sIL2-R and sICAM-I.


CONCLUSIONS
IFN-alpha exerts diverse influences mainly on cytokine antagonists and soluble adhesion molecules. Because sTNF-RII and IL-1RA were increased by IFN-alpha treatment, these might be interesting alternative treatment options in refractory BD. Some of the side-effects of IFN-alpha may be caused by activation of monocytes, which is reflected by an increase in neopterin serum levels.
Kötter
I
I
University Hospital, Department of Internal Medicine II (Haematology, Oncology, Immunology and Rheumatology), Tübingen, Germany. ina.koetter@med.uni-tuebingen.de
Koch
S
S
Vonthein
R
R
Rückwaldt
U
U
Amberger
M
M
Günaydin
I
I
Zierhut
M
M
Stübiger
N
N
D000998:Antiviral Agents / Q000627:therapeutic use*; D001528:Behcet Syndrome / Q000097:blood / Q000188:drug therapy*; D015815:Cell Adhesion Molecules / Q000097:blood*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000097:blood*; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D019798:Neopterin / Q000097:blood; D011994:Recombinant Proteins; D012795:Sialoglycoproteins / Q000097:blood*
D000998:Antiviral Agents; D015815:Cell Adhesion Molecules; D016207:Cytokines; C507763:IL1RN protein, human; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D053590:Interleukin 1 Receptor Antagonist Protein; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D019798:Neopterin