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Previous studies have reported that the mice passively sensitized with anti-DNP IgE antibody exhibited IgE-mediated biphasic cutaneous reaction with an immediate phase response (IPR) at 1 h and a late phase response (LPR) at 24 h after the challenge of DNFB (dinitrofluorobenzene) . We recently found that the third phase inflammatory response with intense and persisting infiltration of eosinophils, named very late phase response (vLPR) , was induced following IPR and LPR in response to DNFB in passively sensitized mice, and that the peak response of vLPR was on the 8^ day after the challenge. The inhibitory effect of Kampo medicines on the triphasic cutaneous inflammatory reaction was divided into several groups in terms of their inhibition rate of ear swelling. Among the formulations, Tokaku-joki-to (Tao-He-Cheng-Qi-Tang) was effective at inhibiting IPR, LPR and vLPR ( +/+/+ group) and scratching behavior in IPR. The Inhibitory effect of Tokaku-joki-to on triphasic cutaneous reaction primarily depends on its composed crude drugs, Glycyrrhizae Radix and Cinnamomi Cortex. These findings indicate that Tokaku-joki-to formulation is usefull for the inhibition of cutaneous inflammatory diseases. 抗DNP IgE抗体で受動感作したマウスの耳介にDNFB(ジニトロフルオロベンゼン)を塗布することにより,1時問およぴ24時間目をピークとする即時相反応(IPR)およぴ遅発相反応(LPR)からなるIgE介在二相性皮膚反応を示すことがすでに知られている。我々は最近,この受動感作マウスにおいてDNFBによる反応惹起後にIPR,LPRに続く,三相目の強い炎症性反応を見出し,超遅発相反応(vLPR)と名付けた。これは抗原塗布から8日目をピークとする,著明かつ持続的な好酸球の浸潤を伴う腫脹反応である。種々の漢方方剤を用いて,この三相性皮膚反応に対する抑制効果を検討した結果,各相の耳介腫脹の抑制率に基づき,いくつかのグループに分類された。検討した方剤中,桃核承気湯はIPR,LPR,vLPRの三相反応に対して抑制を示し(+/+/+群),さらにIPRで観察される耳介の掻き行動(痒みの指標と考えられる)を抑制した。桃核承気湯の三相性皮膚反応に対する抑制効果の発現は,主として構成生薬である甘草およぴ桂皮に基づくことが示唆された。これらの知見から,漢方方剤:桃核承気湯が炎症性皮膚疾患に有効であることが示された。

The pathomechanism of inflammatory bowel disease (IBD) has not yet been fully demonstrated. However, it is well known that mast cells are present in the gastrointestinal tract, suggesting that mast cells may take part in it. So, we investigated the number of mast cells in IBD, such as ulcerative colitis (UC) and eosinophilic colitis, and showed that the number of mast cells was increased in the inflammatory lesions. We also presented a case of UC which was treated successfully with an antiallergic drug, tranilast. Furthermore, possible new approaches to treating the disease with immunomodulators including suplatast are introduced. However, our investigations were performed with a limited number of patients with IBD, and additional further studies are required to confirm the findings.

(1) To clarify the involvement of Th2 responses in the development of allergen-induced airway remodelling, we investigated the effect of anti-CD4 monoclonal antibody (mAb) and anti-CD8 mAb, and the responses of IL-4 gene-knockout (KO) mice in a murine model of allergic asthma. (2) Mice were immunized twice by intraperitoneal injections of ovalbumin (OA), and exposed to aeroallergen (OA, 1% w v(-1)) for 3 weeks. Twenty-four hours after the final challenge, airway responsiveness to acetylcholine was measured, and bronchoalveolar lavage (BAL) and histological examinations were carried out. (3) Anti-CD4 mAb (1 mg kg(-1)) clearly inhibited allergen-induced increases in airway responsiveness to acetylcholine, the number of eosinophils in BAL fluid, serum OA-specific IgE levels, IL-13 and transforming growth factor-beta1 levels in BAL fluid, and amount of hydroxyproline in the lung by 100, 99, 100, 100, 84, and 60%, respectively. Furthermore, the antibody (1 mg kg(-1)) also attenuated allergen-induced goblet cell hyperplasia in the epithelium and subepithelial fibrosis by 72 and 83%, respectively. In contrast, anti-CD8 mAb (1 mg kg(-1)) showed no effect on each parameter. Furthermore, all these parameters were attenuated in IL-4KO mice by 57, 93, 100, 45, 84 and 60%, and also 72 and 83%, respectively. (4) These findings suggest that Th2 responses play a critical role for the development of allergen-induced airway remodelling, and that the inhibition of Th2 responses, e.g. using anti-CD4 mAb, is a therapeutic approach for the treatment of airway remodelling in asthma.

Dark Agouti (DA) and Lewis rat strains were tested for susceptibility to collagen-induced arthritis (CIA) and for development of cellular and humoral immune responses to type II collagen (CII). All of the DA rats developed arthritis following a single intradermal injection of more than 20 microg of CII (130-150 microg/kg rat weight) and showed a swelling rate of more than 100% in the hind paws. The swelling rate showed little deviation among the animals. There was a strong correlation between the severity of the arthritis and the strength of the immune response to CII in DA rats with CIA. Following immunization with even 800 microg of CII (3.8-4.2 mg/kg rat weight), Lewis rats showed a maximum rate of hind paw swelling of only 45%. In the pharmacological studies, prednisolone, indomethacin, FK-506 and mizoribine all suppressed arthritis in DA rats. These findings suggest that DA rats are more susceptible to CIA than Lewis rats and that CIA in DA rats as well as in Lewis rats is serviceable as an experimental animal model of rheumatoid arthritis.