Inability of IL-12 to Down-Regulate IgE Synthesis Due to Defective Production of IFN-γ in Atopic NC/Nga Mice

Abstract

NC/Nga mice raised in nonsterile circumstances spontaneously suffer from atopic dermatitis-like skin lesions with IgE hyperproduction. We investigated effects of rIL-12 on the IgE production in NC/Nga mice. rIL-12 administration was successful to suppress the increase of IgE levels in BALB/c mice immunized with OVA and aluminum hydroxide, but failed to abrogate that in NC/Nga mice. Both in vivo and in vitro IFN-γ production induced by rIL-12 was less in NC/Nga mice than in BALB/c mice. Addition of rIFN-γ to rIL-4 and LPS completely abrogated IgE production by B cells of BALB/c mice, but was insufficient to suppress it by B cells of NC/Nga mice. In splenic cells pretreated with Con A, STAT4 was phosphorylated at the tyrosine residue by addition of rIL-12, which was more weakly inducible in NC/Nga mice than in BALB/c mice. Finally, we examined the preventive ability of rIL-12 on the clinical aspects of atopic dermatitis in NC/Nga mice. rIL-12 administration resulted in exacerbation of development of the skin lesions and IgE production in NC/Nga mice raised in nonsterile circumstances. These results suggest that defective production of IFN-γ by T cells less sensitive to IL-12 and low responsiveness of B cells to IFN-γ may contribute to IgE hyperproduction in NC/Nga mice, and that IL-12 may have no ability to improve the clinical aspects of NC/Nga mice.

Oral Administration of Lactic Acid Bacteria Isolated from Traditional South Asian Fermented Milk `Dahi' Inhibits the Development of Atopic Dermatitis in NC/Nga Mice

“…In NC/Nga mice, serum IgE suppression is reported to be comparatively difficult because they are insensitive to IL-12 compared with BALB/c mice (32,33). Hence it is possible that the R-037 administration could not suppress IgE elevation sufficiently in NC/Nga mice.…”

Prevention of Allergen-Specific, Th2-Biased Immune Responses In Vivo: Role of Increased IL-12 and IL-18 Responsiveness

“…BALB/c mice (widely considered as an "allergic" or type 2-biased mouse strain) have lower basal IL-12 responsiveness than B6 mice (considered a "nonallergic" strain) (29). NC/Nga mice, which spontaneously develop atopic dermatitis and high IgE levels, exhibit substantially impaired IFN-␥ production even following administration of IL-12 (31). The presence of high levels of IL-12 p40 homodimer, a specific antagonist of IL-12 activity, in lung biopsies from asthmatic individuals, but not biopsies from control individuals, suggests that inhibition of local IL-12 activity in the lungs may exacerbate allergic responses by limiting responsiveness to endogenously produced IL-12 (32).…”

Oral Administration of a Hop Water Extract Ameliorates the Development of Dermatitis Induced by the Periodical Topical Application of a Mite Antigen in Atopic Dermatitis Model NC/Nga Mice

“…22) In this present study, IL-12 production from IL-12 production in comparison with the positive control group. Some studies have reported that the development of AD-like skin lesions in NC/Nga mice was associated not only with the Th2 cell-mediated response but also with the Th1 cell-mediated response.…”

“…Some studies have reported that the development of AD-like skin lesions in NC/Nga mice was associated not only with the Th2 cell-mediated response but also with the Th1 cell-mediated response. 14,22,23) An intraperitoneal administration of rIL-12 or rIFN-has shown an exacerbating effect on the progression of skin lesions in conventional NC/Nga mice, and rIL-12 administration increased the IgE level in serum. 22) For these reasons, the inhibition of IgE production in NC/Nga mice by the oral administration of HWE might have been partly due to the inhibition of IL-12 production.…”

“…14,22,23) An intraperitoneal administration of rIL-12 or rIFN-has shown an exacerbating effect on the progression of skin lesions in conventional NC/Nga mice, and rIL-12 administration increased the IgE level in serum. 22) For these reasons, the inhibition of IgE production in NC/Nga mice by the oral administration of HWE might have been partly due to the inhibition of IL-12 production. IL-12 has been produced from activated macrophage and dendritic cells in response to many microbial stimuli.…”