Search

We have shown previously that in addition to IL-4, IL-5 and IL-10, antigen-specific interferon-gamma (IFN-gamma) production by spleen cells from ovalbumin (OVA)/Alum-immunized mice is inhibited by the administration of royal jelly (RJ). Since it has been shown that both Th1 and Th2 cytokines play pathogenic roles in the generation of atopic dermatitis (AD), we have examined whether RJ suppresses the development of AD-like skin lesions in NC/Nga mice induced by repeated application of picryl chloride (PiCl) under specific pathogen-free (SPF) conditions. Oral administration of RJ to the PiCl-treated NC/Nga mice inhibited the development of AD-like skin lesions in these mice as exemplified by the significant decrease in the total skin severity scores and the decrease in hypertrophy, hyperkeratosis, and infiltration of the epidermis and corium by inflammatory cells. IFN-gamma production by spleen cells from PiCl-treated NC/Nga mice in response to TNP-KLH was partially but significantly inhibited by the oral administration of RJ, while IFN-gamma production by Con A-stimulated spleen cells was not affected. Since inducible nitric oxide (NO) synthase (iNOS)-derived NO has been suggested as an important immunoregulatory mediator in inflammatory autoimmune diseases, we have also examined the expression of iNOS in the dorsal skin lesions of PiCl-treated NC/Nga mice. Interestingly, the expression of iNOS was significantly increased in the skin lesions of RJ-administered mice compared with those of control PBS-administered mice. Thus, our results suggest that RJ suppresses the development of AD-like skin lesions in PiCl-treated NC/Nga mice, possibly by a combination of down-regulating TNP-specific IFN-gamma production and up-regulating iNOS expression.

We have here examined the immunoregulatory effects of a natural flavonoid, Kaempferol, on T cells. Kaempferol suppressed IFN-gamma and IL-2 production but not that of IL-4 by T cells and shifted the Th1/Th2 balance into the Th2 phenotype. In C57BL/6 anti-BDF1 MLC, Kaempferol inhibited the development and expansion of type 1 effector CD8+ T cells and diminished allospecific CTL activity. Based on these in vitro results, we evaluated the effects of Kaempferol treatment on the development of C57BL/6-into-BDF1 acute graft-versus-host disease (GVHD). Brief administration of Kaempferol led to early recovery from body weight loss, increased survival, and reduced tissue injury in the liver and large intestine. Kaempferol treatment activated Th2 cells and the engraftment of donor cells and also diminished GVHD-associated antihost CTL activity. Thus, our study indicates that Kaempferol has the capacity to modulate the Th1/Th2 balance and could be useful for the treatment of cell-mediated immune diseases, such as acute GVHD., ((c) 2002 Elsevier Science (USA).)

We investigated the Diels-Alder reactions of maleic anhydrides embedded in a dibenzobicyclo[2.2.2]octatriene motif as a nonsterically biased dienophile. Substituents on a benzene ring in these dienophiles are far from the reaction center, providing a sterically equivalent pi-face. Instead substituents can unsymmetrize the dienophilic pi face through pi (anhydride)-pi (aromatic) orbital interactions. Electron-withdrawing substituents affect the facial bias and relative rates of these cycloadditions. The preference of the cycloadditions is opposite in direction to those observed in nucleophilic additions of 2-substituted-9,10-dihydro-9,10-ethanoanthracen-11-ones (dibenzobicyclo[2.2.2]octadienones) and in electrophilic additions of 2-substituted 9,10-dihydro-9,10-ethenoanthracenes (dibenzobicyclo[2.2.2]octatrienes), though all of them have related dibenzobicyclic systems.