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Ingested IFN- has biological effects in humans with relapsing-remitting multiple sclerosis

Department of Neurology, University of Texas-Houston, Health Science Center, PO Box 20708, Houston, Texas 77225, USA

Ronald H Kerman

Division of Immunology and Organ Transplantation, Department of Surgery, University of Texas-Houston, Health Science Center, PO Box 20708, Houston, Texas 77225, USA

Laura D Nelson

Department of Neurology, University of Texas-Houston, Health Science Center, PO Box 20708, Houston, Texas 77225, USA

Gailen D Marshall, JR

Department of Internal Medicine, University of Texas-Houston, Health Science Center, PO Box 20708, Houston, Texas 77225, USA

Evelyn M Henninger

Department of Internal Medicine, University of Texas-Houston, Health Science Center, PO Box 20708, Houston, Texas 77225, USA

Mohammed Khan

Department of Neurology, University of Texas-Houston, Health Science Center, PO Box 20708, Houston, Texas 77225, USA

Rui Jin

Department of Neurology, University of Texas-Houston, Health Science Center, PO Box 20708, Houston, Texas 77225, USA

Jerry S Wolinsky

Department of Neurology, University of Texas-Houston, Health Science Center, PO Box 20708, Houston, Texas 77225, USA

Parenterally administered human recombinant type I interferons (hrIFN) in relapsing-remitting multiple sclerosis (RRMS) decrease relapses and spontaneous in vitro IFN- production, reduce clinical progression, and decrease magnetic resonance imaging (MRI)-defined disease activity and lesions. Parenterally administered type I IFN use is limited by clinical and chemical toxicities, and the induction of antibodies that abrogate their activity in vivo correlated with the loss of clinical benefit. Therefore, we determined whether ingested IFN- was non-toxic and had biological effects in humans. ingested hrIFN- showed no toxicity in normal volunteers or patients with RRMS at doses ranging from 300 to 100 000 units. In subjects with RRMS, a significant decrease in Con A-mediated proliferation and serum soluble intercellular adhesion molecule-I (sICAM-I), a surrogate measure for disease activity in MS, was found after ingesting 10 000 and 30 000 units IFN- The RRMS subjects also showed decreased IL-2 secretion after ingesting 10 000 units IFN-, and decreased IFN-, TGF-β and IL-10 production after ingesting 30 000 units IFN-. The decreased secretion of IFN- and IL-2 by ingested IFN- suggests that oral IFN- may cause a functional inhibition of Th I-like T helper cells in RRMS, a potential site of intervention at the level of effector T cells in MS. Our studies support the oral use of human IFN- as a biological response modifier in humans.

Key Words: multiple sclerosis • oral administration • IFN- • IFN- • gut associated lymphoid tissue (GALT)

Multiple Sclerosis, Vol. 3, No. 1, 1-7 (1997)
DOI: 10.1177/135245859700300101


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