The high correlation between the IgG isotype of anticardiolipin antibodies (aCLs) and clinical thrombosis was first documented in 1983, and this observation was confirmed in subsequent studies. In addition, the frequency of fetal loss and thrombocytopenia was increased in this group of patients. These findings led in 1986 to recognition of the so-called anticardiolipin syndrome, later termed the antiphospholipid syndrome (APS) . This syndrome was seen mostly in patients with systemic lupus erythematosus (SLE), but it soon became clear other patients not suffering from defined SLE might exhibit features of APS.
aCL found in APS patients are detected in immunoassays using solid phase cardiolipin as a putative antigen. However, antibodies directed against phospholipid-binding plasma or serum proteins, in particular, β2-glycoprotein I (β2 GPI), are also detected. Many recent studies indicated that one of predominant antibodies have been realized as aCL in APS patients are against β2 GPI rather than any of negatively charged phospholipids. We reported that the epitopes recognized by anti-β 2 GPI antibodies raised in APS patients are composed of discontinuous amino acid sequences from the IV domain of human β2 GPI. These epitopes are crvntic when β2 GPI is not interacted with anionic nhosnholmids.
An early event in atherosclerosis is the accumulation of cholesterol-laden foam cells, which originate mainly from monocyte-macrophage cells, by their uptake of chemically modified LDL. We found that β2 GPI directly binds to oxLDL and that the complex of oxLDL and β2 GPI is subsequently recognized by aCL (anti-β2 GPI) to be taken up by macrophages.
Antibodies against phosphatidylserine-prothrombin complex (aPS/PT) are closely associated with APS and lupus anticoagulant. aPS/PT can be one of the strong markers of APS as well as aCL (anti-β2 GPI), considering the correlation between aPS/PT and APS with very high specificity. We proposed that aPS/PT should be performed in conjunction with the other aPL detections to improve the likelihood of recognizing APS, ultimately ameliorating the management for the affected patients.
International consensus statement on classification criteria for APS and the standard therapeutic strategy for this syndrome are also described in this review.

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Atopic deramtitis is characterized immunologically by the expression of Th 2 cytokines including interleukin-4 and 5 at the initiation phase of inflammation after percutaneous penetration of causative allergens and by the expression of Th 1 cytokines such as interferon-gamma at the late maintenance phase. The inflammation in atopic dermatitis is supported by the presence of a variety of inflammatory cells including T cells, eosinophils, mast cells, Langerhans cells and/or epidermal cells and fibroblasts.
In order to achieve quick and dramatic elimination of inflammation, pharmaceutical agents having capacities to down-regulate the activation of majority of participating cells such as steroids and immunosuppressants including cyclosporin and FK 506 : tacrolimus are clinically useful.

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Toll in Drosophila is a receptor that is required for dorsoventral polarity during development, and also involved in host defence against fungal infection. Recently, mammalian homologues of Toll, designated as Toll-like receptors (TLRs) have been identified. The TLR family harbors an extracellular leucine-rich repeat (LRR) domain and a cytoplasmic domain that is homologous to that of the IL-1R family. Analogous to the IL-1R, TLR recruits IRAK via adaptor MyD88, and then induces activation of TRAF6, NIK and finally NF-κB.
In order to examine the role of TLR family, we have generated mice lacking TLR2, TLR4, and MyD88. TLR4 KO mice are hyporesponsive to LPS. On the other hand, TLR2 KO mice are hyporesponsive to peptidoglycan from gram-positive bacteria, but not to LPS. MyD88 KO mice are unresponsive to LPS. Taken together, these results demonstrate that responses to bacterial cell wall components are differentially mediated by TLR2 and TLR4, and that LPS signaling is mediated by TLR4 via MyD88.

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CD 26/dipeptidyl peptidase IV (DPPIV) is a cell surface ectoenzyme which participates in immune and inflammatory reactions. We found that CD 26 was only partially expressed on human fibroblasts from periodontal tissues, whereas fibroblasts from lung and skin expressed CD 26 constitutively as revealed by flow cytometry. We examined the possible upregulation of CD 26-expression on human gingival fibroblasts in response to various stimulants. Interleukin (IL) -1 α, tumor necrosis factor (TNF) -α, interferon (IFN) -γ, lipopolysaccharide (LPS) from Porphyromonas gingivalis, Prevotella intermedia, and Escherichia coli and Prevotella glycoprotein augmented CD 26 expression on gingival fibroblasts. Among the stimulants, IL-1 α exhibited the most potent activity. Enzymatic activity of CD 26 was also induced by stimulation on fibroblasts. The upregulation of CD 26 mRNA expression upon stimulation with IL-1 α was also revealed by a quantitative RT-PCR assay. In the kinetic experiment, 48 h and several days were required for maximum CD 26 mRNA accumulation and CD 26 molecule expression on the cell surface, respectively. The addition of cycloheximide almost completely inhibited the accumulation of CD 26 mRNA induced by IL-1 α. These results suggested that induction of CD 26 on human gingival fibroblasts is regulated at the transcriptional level, and is also dependent on a de nove synthesized protein factor (s) .

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To study the inflammatory responses of small airway epithelium in various airway disorders, we harvested living epithelial cells from very peripheral airways by employing a new ultrathin fiberscope. The expression levels of IL-8 or eotaxin when evaluated by reverse transcription-polymerase chain reaction (RT-PCR) were significantly increased in COPD and asthma respectively. We also studied the gene expression of transforming growth factor (TGF) -β-1, a potent fibrogenic factor, in small airway epithelium from smokers and patients with COPD. The expression levels of TGFβ-1 were elevated in smoking group and COPD than in non-smokers. Furthermore, TGFβ-1 mRNA levels correlated with the degrees of small airway obstruction as assessed by the measurements of flow-volume curves. Finally, we evaluated the growth responses of these cells to a veriety of growth factors, and found that hepatocyte growth factor (HGF) positively, and TGFβ-1 negatively regulated their proliferation in vitro.
In conclusions, this approach with a new ultrathin bronchofiberscope promised as a good tool for evaluation of cellular and molecular changes in the small airways.

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Cryptococcus neoformans, a ubiquitous fungal pathogen, causes a life-threatening infection in patients with AIDS. Host defense to this pathogen is mediated by cellular immunity, which receives a critical regulation by a balance between Th 1 cytokines, such as IFN-γ, and Th 2 cytokines, including IL-4 and IL-10. Overproduction of Th 1 cytokines relative to Th 2 cytokines protects host against this microbe, while shifted balance toward Th 2 cytokines is related to exacerbation of this infection. This balance is controled by IL-12 secreted by macrophages. In the present study, using a murine model of pulmonary and disseminated infection with C. neoformans, we demonstrated the shifted balance between these two categories of cytokines toward Th 2-dominant state in lung, which resulted in the uncontroled infection. Interestingly, IL-12 treatment altered this balance toward Th 1-dominant condition and protected animals from the fatal infection. We also demonstrated the failure of mononuclear leukocytes-trafficking chemokines, including RANTES, MCP-1, MIP-1 α, β and IP-10, to be produced, which resulted in poor infiltration of protective inflammatory leukocytes in lung after infection with C. neoformans. IL-12 treatment induced marked accumulation of these cells through production of the above chemokines. Finally we showed the suppressive effects of C. neoformans on IL-12 production by macrophages stimulated with LPS and IFN-γ. These results suggested that C. neoformans may suppress the induction of Th 1 responses by inhibiting macrophage IL-12 production. This mechanism may allow the fungal pathogen to evade the host defense system.

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Whether the apheresis have an anti-inflammatory effect on adjuvant arthritis rats was investigated. The apheresis with Gossypium barbadense cotton and polysulfon filters were done 4 days after immunization with complete adjuvant. Blood was drawn continuously from the tail's artery and introduced into the syringe which contained the filter, and returned to the tail's artery. Three milliliter of whole blood was processed in one time and it was repeated 5 times. In total, 15 ml of whole blood was processed. In laboratory values, WBC from apheresis group showed a higher value level than those from control group, though leukapheresis removed substantial leukocytes. Hemoglobin, hematocrit, platelets and RBC were lower level at 21 days after immunization. The apheresis with Gossypium barbadense cotton showed marked inhibition of swelling and bone destruction in hind legs in rats, and the apheresis with bio-compatible filter, polysulfon also showed marked inhibition of swelling.

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A 64 year-old man visited our hospital with chronic lumbago. On physical examination there was no remarkable findings, but laboratory data presented accelerated erythrocyte sedimentation rate and elevated C-reactive protein level. Abdominal computed tomography (CT) scan showed abdominal aortic aneurysm with thick wall at lower level of renal artery bifurcation. On the enhanced CT scan slight enhancement of the aneurysmal wall which is so-called “mantle sign” was present. Complicated two sacculated aneurysm were shown at the left common iliac artery by intravenous-digital subtraction angiography. Common iliac artery aneurysms were resected because of a risk of rupture. In the operation, strong fibrous changes involving the left ureter from the abdominal aorta to the left common iliac artery were found. Postoperative pathological examination of saccular aneurysm showed no findings of inflammation. A diagnosis of IAAA was made clinically on the basis of clinical findings, laboratory data and image studies without pathological aortic lesion.

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We report a 30 years old systemic lupus erythematosus (SLE) female patient, who had been diagnosed with systemic Weber Christian disease, presented with acute onset of high fever, hepatomegaly, lower leg edema with multiple subcutaneous nodules. Laboratory tests showed elevated CRP, fibrinogen and liver enzymes, especially LDH and LAP, with coagulation abnormalities. There is a marked enlarged fatty liver in both abdomen echo and CT and chest X-ray films showed pleural effusion in both sides, without pulmonary lesions. However, complements, ANA and anti-DNA antibody etc concerning activity of SLE didn't moved. A diagnosis of systemic Weber Christian disease was made based on clinical and laboratory examinations and histopathological findings. The therapy of standard treatment, such as steroid, plus pulse steroid therapy was performed. The response, however, is unpredictable. After this, tacrolimus hydrate was administed intravenously in an initial dose of 1.2 mg/body and in oral maintenance of 1.0 mg/ body with a drastic response and patient completely recovered within 1 month. To our knowledge, this is the first report of SLE complicated systemic Weber Christian disease and is the first report of successful treatment of systemic Weber Christian disease with tacrolimus hydrate.

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