Abstract
Byline: Mustafa G. Mujtaba, Lorelie Villarete, Howard M. Johnson Keywords: IFN; IgE; ovalbumin; mouse; human myeloma; lung; infiltration; inhibition Abbreviations: EAE, Experimental allergic encephalomyelitis; HRP, Horseradish peroxidase; OVA, Ovalbumin Background: IFN-I, a type I IFN, is an antiviral, immunomodulating, and antiproliferative agent similar to IFN-[alpha] and IFN-[beta], but IFN-I lacks the toxicity associated with high concentrations of these IFNs in tissue culture and in animal studies. We have previously shown that IFN-I inhibits antibody production in a murine model of an autoimmune disease. Objective: We investigate the effectiveness of ovine IFN-I and other type I IFNs in suppressing the development of allergic sensitization in a murine model of allergy by using ovalbumin (OVA) antigen as an allergen and in suppressing IgE production by using a human IgE-producing myeloma cell line. Methods and Results: Mice that were treated with IFN-I in vivo before and after intraperitoneal immunization with aluminum hydroxide-precipitated OVA had significantly lower OVA-specific IgE levels than the PBS-treated group. IFN-I-treated mice had reduced inflammatory cell infiltration into the lung tissue. Furthermore, in vitro IFN-I treatment of splenocytes taken from OVA-immunized mice suppressed OVA-induced proliferation. Also, treatment of the IgE-producing human myeloma cell line U266BL with IFN-I-reduced IgE production and inhibited cell proliferation compared with media controls. Similar suppression of proliferation and inhibition of IgE production was seen with other type I IFNs, as well as a humanized IFN-I/IFN-[alpha]D chimeric that consists of residues 1 to 27 of the ovine IFN-I and residues 28 to 166 of the human IFN-[alpha]D. The chimeric was not toxic to human peripheral white blood cells at concentrations as high as 10.sup.5 U/mL, whereas human IFN-[alpha]D was toxic at 10.sup.3 U/mL. Conclusion: These data suggest that IFNs may be useful in preventing allergic sensitization by suppressing the production of allergen-specific IgE antibodies without toxic side effects. (J Allergy Clin Immunol 1999;104:1037-44.) Author Affiliation: Gainesville, Fla, and Alameda, Calif From.sup.athe Department of Microbiology and Cell Science, University of Florida, Gainesville; and.sup.bPepgen Corp, Alameda Article History: Received 1 March 1999; Revised 9 June 1999; Accepted 15 July 1999 Article Note: (footnote) [star] Supported by grants CA69959 and R37AI25904 to H. M. J. This manuscript is Florida Agriculture Experiment Station Journal Series R-07085., [star][star] Reprint requests: Mustafa Mujtaba, BS, Department of Microbiology and Cell Science, University of Florida, Bldg 981, Room 1052, Gainesville, FL 32611., a 0091-6749/99 $8.00 + 0 1/1/101655