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In the version of this article initially published, the fourth image in Figure 4b was a duplication of the third image. The error has been corrected in the HTML and PDF versions of the article.nature medicine volume 16 | number 11 | november 2010 1341 e r r ata

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This study was designed to evaluate whether the sequential monitoring of serum interleukin-6 levels (SIL-6) could be helpful for diagnosing the occurrence of hepatic allograft rejection. An SIL-6 post-transplant study was conducted on nine cynomolgus monkeys which had undergone orthotopic hepatic allotransplantation, six of which were treated with FK-506 (a new immunosuppressant agent isolated from Streptomyces tsukubaensis) and three of which were not. All the nontreated animals showed biochemical abnormalities from days 5-6, characterized by a marked elevation of serum alkaline phosphatase levels, and they eventually died on days 8, 12, and 63 (group I). Acute cellular rejection was confirmed by histological study of the hepatic grafts taken at autopsy or biopsy. On the other hand, four of the treated animals (group IIa) survived more than 30 days. Biochemical examination of this group showed no abnormal signs apart from a slight elevation of alkaline phosphatase (< 2000 IU/l). Histological examination carried out around 30 days after transplantation revealed a transient infiltration of polynuclear cells into Glisson's area, with the portal vein and bile duct remaining intact. The remaining two animals (group IIb) died of dehydration and arterial thrombosis on days 5 and 7, respectively. A kinetic study of SIL-6 conducted during the first 2 weeks showed quite different patterns among the three groups. All recipients in group I demonstrated two peaks following grafting on days 1 and 3 or 4, the second peak of above 2.0 U/ml preceding biochemical abnormalities by 2 to 3 days.(ABSTRACT TRUNCATED AT 250 WORDS)

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BackgroundRheumatoid arthritis (RA) is a common immflamatory autoimmune disease characterized by persistent synovitis and progressive destruction of cartilage and bone in multiple joints. The proportion of CD25+CD4+ T cells is increased in anti-citrullinated protein antibodies (ACPA) positive RA patients compared with ACPA negative RA patients. Abatacept (ABA), a biologic blocking T cell co-stimulation, decreased the proportion of CD25+CD4+ T cells and interleukin (IL)-6 levels in ACPA positive RA patients. It has been reported that CD25 expressions are increased by IL-6. Tocilizmab (TCZ) is a humanized anti-human IL-6 receptor antibody that has been developed to inhibit the IL-6 signal as a therapeutic agent.ObjectivesWe aimed to investigate whether IL-6 blockade with TCZ decreases the proportion of CD25+CD4+ T cells.MethodsPeripheral blood mononucleated cells (PBMCs) were obtained from 13 ACPA (+) RA patients at baseline, 24 and 48 weeks of TCZ treatment (male:female ratio = 0.077). Surface phenotypes and activation markers of T cells were analyzed with flow cytometory.ResultsDAS28-ESR and SDAI were significantly reduced at 24 and 48 weeks compared with those at baseline (DAS28-ESR: 4.87±1.25 at baseline; 1.99±1.13 at 24 weeks, p<0.0001; 1.61±0.70 at 48 weeks p<0.0001; SDAI: 20.75±9.56 at baseline; 6.30±7.0 at 24 weeks,p=0.0008; 3.20±2.86 at 48 weeks, p<0.0001). The serum levels of matrix metalloproteinase (MMP)-3 were significantly decreased at 48 weeks (250.5±311.0 ng/mL at baseline; 85.1±81.8 ng/mL at 24 weeks, p=0.07; 54.9±27.2 ng/mL at 48 weeks, p=0.04). The proportion of CD4+ cells was significantly increased at 24 and 48 weeks compared with those at baseline (29.7±18.2% at baseline; 37.3±12.9% at 24 weeks, p=0.0094; 37.7±14.1% at 48 weeks, p=0.025). The proportions of CD25+CD4+ cells in CD4+ cells were not significantly different (5.7±4.2% at baseline; 6.1±3.4% at 24 weeks, p=0.795; 7.1±2.1% at 48 weeks, p=0.247). Also, the proportions of regulatory T (Treg) cells (FoxP3+CD25+CD4+ in CD4+ cells) were not significantly different (0.68±0.67% at baseline; 0.58±0.52% at 24 weeks p=0.752; 0.61±0.53% at 48 weeks, p=0.794).ConclusionsIL-6 blockade has therapeutic effects on RA patients. However, the blockade does not change proportions of CD4+CD25+ in CD4+ T cells as well as those of Treg cells. Some other mechanisms, besides a decrease in CD4+ activation or an increase in Treg cell proportion, contribute the therapeutic effect of IL-6 blockade.Disclosure of InterestM. Murakami Grant/research support from: Chugai Pharmaceutical Co., Ltd., T. Kuritani: None declared, N. Nishimoto Grant/research support from: Chugai Pharmaceutical Co., Ltd., Consultant for: Chugai Pharmaceutical Co., Ltd.