Mujtaba M G, Villarete L, Johnson H M
Department of Microbiology and Cell Science, University of Florida, Gainesville 32611, USA.
J Allergy Clin Immunol. 1999 Nov;104(5):1037-44. doi: 10.1016/s0091-6749(99)70086-2.
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.
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.
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.
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.
Ⅰ型干扰素τ与干扰素α和干扰素β类似，是一种抗病毒、免疫调节和抗增殖剂，但在组织培养和动物研究中，干扰素τ缺乏与高浓度这些干扰素相关的毒性。我们之前已经表明，干扰素τ在自身免疫性疾病的小鼠模型中可抑制抗体产生。
我们通过使用卵清蛋白（OVA）抗原作为过敏原，研究绵羊干扰素τ和其他Ⅰ型干扰素在小鼠过敏模型中抑制过敏致敏发展的有效性，以及通过使用产生人IgE的骨髓瘤细胞系来研究其抑制IgE产生的有效性。
在用氢氧化铝沉淀的OVA进行腹腔免疫前后，体内接受干扰素τ治疗的小鼠的OVA特异性IgE水平显著低于接受PBS治疗的组。接受干扰素τ治疗的小鼠肺组织中的炎性细胞浸润减少。此外，体外使用干扰素τ处理从OVA免疫小鼠获取的脾细胞可抑制OVA诱导的增殖。而且，与培养基对照相比，用干扰素τ处理产生IgE的人骨髓瘤细胞系U266BL可降低IgE产生并抑制细胞增殖。其他Ⅰ型干扰素以及由绵羊干扰素τ的1至27位残基和人干扰素αD的28至166位残基组成的人源化干扰素τ/干扰素αD嵌合体也观察到了类似的增殖抑制和IgE产生抑制。该嵌合体在高达10⁵ U/mL的浓度下对人外周白细胞无毒，而人干扰素αD在10³ U/mL时有毒。
这些数据表明，干扰素可能通过抑制过敏原特异性IgE抗体的产生而无毒性副作用，从而有助于预防过敏致敏。
