Ingested IFN-alpha has biological effects in humans with relapsing-remitting multiple sclerosis.
Parenterally administered human recombinant type I interferons (hrIFN) in relapsing-remitting multiple sclerosis (RRMS) decrease relapses and spontaneous in vitro IFN-gamma 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-alpha was non-toxic and had biological effects in humans. Ingested hrIFN-alpha 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-1 (sICAM-1), a surrogate measure for disease activity in MS, was found after ingesting 10,000 and 30,000 units IFN-alpha The RRMS subjects also showed decreased IL-2 secretion after ingesting 10,000 units IFN-alpha and decreased IFN-gamma, TGF-beta and IL-10 production after ingesting 30,000 units IFN-alpha. The decreased secretion of IFN-gamma and IL-2 by ingested IFN-alpha suggests that oral IFN-alpha may cause a functional inhibition of Th J-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-alpha as a biological response modifier in humans.
Brod
S A
SA
Department of Neurology, University of Texas-Houston, Health Science Center 77225, USA.
Kerman
R H
RH
Nelson
L D
LD
Marshall
G D
GD
Henninger
E M
EM
Khan
M
M
Jin
R
R
Wolinsky
J S
JS
D000284:Administration, Oral; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D009000:Monocytes / Q000473:pathology; D009103:Multiple Sclerosis / Q000097:blood / Q000503:physiopathology* / Q000628:therapy*; D011994:Recombinant Proteins; D016896:Treatment Outcome
D018836:Inflammation Mediators; D016898:Interferon-alpha; D011994:Recombinant Proteins; D003208:Concanavalin A; D018799:Intercellular Adhesion Molecule-1