IFN-tau 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, immunomodulating, 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
We 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.


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-alphaD chimeric that consists of residues 1 to 27 of the ovine IFN-tau and residues 28 to 166 of the human IFN-alphaD. The chimeric was not toxic to human peripheral white blood cells at concentrations as high as 10(5) U/mL, whereas human IFN-alphaD was toxic at 10(3) U/mL.


CONCLUSIONS
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.
Mujtaba
M G
MG
Department of Microbiology and Cell Science, University of Florida, Gainesville 32611, USA.
Villarete
L
L
Johnson
H M
HM
D000818:Animals; D000917:Antibody Formation; D002417:Cattle; D002455:Cell Division; D004195:Disease Models, Animal; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000097:blood; D007370:Interferon Type I / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016898:Interferon-alpha / Q000276:immunology / Q000633:toxicity; D015847:Interleukin-4 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011257:Pregnancy Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000097:blood / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D012756:Sheep; D013154:Spleen / Q000166:cytology; D014407:Tumor Cells, Cultured
D007370:Interferon Type I; D016898:Interferon-alpha; D011257:Pregnancy Proteins; D011993:Recombinant Fusion Proteins; C020947:interferon tau; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin