IFN-τ inhibits IgE production in a murine model of allergy and in an IgE-producing human myeloma cell line

Background: IFN-tau, a type I IFN, is an antiviral, immunomadulating, and antiproliferative agent similar to IFN-alpha and IFN-beta, but IFN-tau lacks the toxicity associated with high concentrations of these IFNs in tissue culture and in animal studies. We have previously shown that IFN-tau inhibits antibody production in a murine model of an autoimmune disease, Objective: me investigate the effectiveness of ovine IFN-tau 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-tau 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-tau-treated mice had reduced inflammatory cell infiltration into the lung tissue. Furthermore, in vitro IFN-tau 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-tau-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-tau/IFN-alpha D chimeric that consists of residues 1 to 27 of the ovine IFN-tau 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(5) U/mL, whereas human IFN-alpha D was toxic at 10(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.