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High-dose infusion of IgG (IVIG) is used to treat autoimmune and inflammatory diseases, including Kawasaki disease (KD). Although the immunomodulatory effects of IVIG on blood cells such as macrophages have been well studied, its effects on tissue cells remain unclear. Here, we show that high-dose IgG specifically and completely inhibited TNF-α-induced, but not IL-1β-induced, secretion of proinflammatory cytokines such as G-CSF and IL-6 by cultured human coronary artery endothelial cells (HCAECs). High-dose IgG did not inhibit TNF-α-mediated early signaling events of the NF-κB and MAPK pathways but it potently inhibited gene expression of G-CSF and IL-6 12 h after TNF-α-stimulation. Interestingly, suppression of the G-CSF and IL-6 gene expression correlated closely with functional inhibition of a transcription factor, C/EBPδ, whose binding sites in the promoters of G-CSF and IL-6 have been shown to be critical for their transcriptional activation. Furthermore, the inhibitory effect of intact IgG on HCAECs was exerted mainly via its F(ab’)2 fragment, and not its Fc fragment. These findings suggest that the clinical effects of IVIG on KD patients are at least in part due to its direct anti-inflammatory effects on the coronary endothelium, which is a major lesion site in the pathogenesis of KD.

High-dose infusion of IgG (IVIG) is used to treat autoimmune and inflammatory diseases, including Kawasaki disease (KD). Although the immunomodulatory effects of IVIG on blood cells such as macrophages have been well studied, its effects on tissue cells remain unclear. Here, we show that high-dose IgG specifically and completely inhibited TNF-α-induced, but not IL-1β-induced, secretion of proinflammatory cytokines such as G-CSF and IL-6 by cultured human coronary artery endothelial cells (HCAECs). High-dose IgG did not inhibit TNF-α-mediated early signaling events of the NF-κB and MAPK pathways but it potently inhibited gene expression of G-CSF and IL-6 12 h after TNF-α-stimulation. Interestingly, suppression of the G-CSF and IL-6 gene expression correlated closely with functional inhibition of a transcription factor, C/EBPδ, whose binding sites in the promoters of G-CSF and IL-6 have been shown to be critical for their transcriptional activation. Furthermore, the inhibitory effect of intact IgG on HCAECs was exerted mainly via its F(ab')(2) fragment, and not its Fc fragment. These findings suggest that the clinical effects of IVIG on KD patients are at least in part due to its direct anti-inflammatory effects on the coronary endothelium, which is a major lesion site in the pathogenesis of KD.

血液透析患者に合併した化膿性心外膜炎の2症例を経験した.症例1は約2年間, 症例2は約6か月間の安定した血液透析を受けていた. 持続的発熱, 胸部X線写真で心陰影の拡大を指摘され, 心エコー検査で大量の心嚢液の貯留を認めた. 症例2はショックのため入院後比較的短期間で死亡した. 症例1は持続的心嚢液排液, 心嚢開窓術を施行, 血液膿汁からEnterobacterが検出された. 排液不良のため心不全で死亡した. 剖検ではいずれも心外膜の線維性肥厚, 膿瘍形成を認め化膿性心外膜炎と診断した. さらに肝, 脾にも膿瘍を形成しており, 敗血症の存在が考えられた. 長期間の安定した血液透析を受けていたが心外膜炎を合併し, さらに敗血症のために化膿性心外膜炎を併病するに至ったと考えられる. 早期の診断および可及的外科的処置が必要と考えられた.

Keeping the pH constant during the incubation of sample and complement solutions was an inportant factor to obtain a reproducibla ACA value. Lyophilized complement shows a pH of 8.8-9.0 after reconstitution. The pH of frozen complement is 7.2-7.4. When the ACA of an intravenous IgG (IVIG) was tested with the reconstituted complement, the ACA value was higher than when the preparation was tested with frozen complement.Ionic strength also affected the ACA test of an IVIG which did not contain ionic substances such as NaCl or glycine. Even when the pH and ionic strength of commercial IVIG preparations were standardized by dialysis, the concentration of IgG polymer did not necessarily correlate with the ACA value.

Fibronectin (Fn) has been shown to play an important role in wound healing because it appears to be the stimulus for migration of fibroblasts and epidermal cells. The purpose of this study was to investigate whether topical application of plasma Fn (pFn) improves healing of full-thickness skin wounds in rats. A round section of full-thickness skin (diameter of approximately 15 mm) was resected in rats. Animals were then divided into two groups, and wounds were treated topically with a single application of human plasma albumin (control group) or human pFn (FN group). Wound closure rate, hydroxyproline concentration, and histologic features (immunohistochemical staining) were evaluated. The FN group had a significantly higher wound closure rate and hydroxyproline level in the skin than the control group. Histologic analysis of macrophage and fibroblast migration, collagen regeneration, and epithelialization were significantly increased in the FN group compared with the control group. A single topical application of pFn increased the migration of macrophages, myofibroblasts, and fibroblasts. Moreover, further release of transforming growth factor-beta1 from activated fibroblasts, keratinocytes, and epithelial cells may also contribute to the beneficial effect of pFn on wound healing.

A method for the heat treatment of human IgG solution at 60 degrees C for 10 h was established. Human immunodeficiency, mumps, vaccinia and 4 other viruses were added to the IgG solution in 33% sorbitol and heated at 60 degrees C. Those viruses were inactivated within 1 h. Heat-treated intravenous IgG (IVIG-H) was prepared by heat treatment and polyethylene glycol (PEG) fractionation. Conventional nonheated intravenous IgG (IVIG-C) was prepared from the same source paste by the fractionation method. No physicochemical or biological difference was observed between the heated and control IVIG preparations.

Before HBsAg screening of plasma was instituted, the preventive effect of immunoglobulin preparations (ISG) against Hepatitis B was not clearly defined. Since HBsAg screening became a requirement, all ISG has shown Anti-HBs and it further became clear that such preparations are effective in preventing Hepatitis B.Recently, cases of Hepatitis NANB associated with administration of intravenous immunoglobulin (IVIG) were reported. Since there is no NANB screening test presently available and IVIG tends to be administered in a large volume, a virus inactivation treatment should be performed on IVIG.Now that heat treatment at 60°C for 10 hours, which had previously been considered to be impossible or unnecessary for immunoglobulin, has become possible, an intravenous immunoglobulin preparation which is more ideal in stability and safety is available.