PMC4857353_01
(a) X-ray images of the left toe from the patient with tophaceous gout. The tophus of the left first MTP joint and the overhanging margin (arrows) before tocilizumab treatment (Before) are shown. The tophus of the left first MTP joint decreased in size after tocilizumab treatment for 24 weeks (After). (b) Medications are indicated, and concomitant body temperature, serum CRP, serum UA and serum IL-6 concentrations are plotted by blue circle, red square, green triangle and black diamond, after admission. (c) IL-1beta, TNF-alpha, IL-6, and IL-8 secretions by peripheral blood mononuclear cells (PBMCs) derived from the patient with tophaceous gout (Gout patient) and PBMCs from two healthy volunteers (Control1 and Control2). Isolated PBMCs were incubated with the indicated amount of muramyl dipeptide (MDP) (10 ng/mL or 1 microg/mL), lipopolysaccharide (LPS) (0.1 ng/mL or 10 ng/mL), MDP (10 ng/mL or 1 microg/mL) combined with LPS (0.1 ng/mL) or were left untreated (-) for 8 h. The concentrations of IL-1beta, TNF-alpha, IL-6, and IL-8 in the supernatants were measured by ELISA. Values are the mean and SD from triplicate cultures. (d) Expression of inflammasome components in tophus with urate crystals excided from the left elbow. Expressions of cryopyrin (Cryopyrin), ASC (ASC), caspase-1 (Caspase-1), and IL-1beta (IL-1beta) were detected by immunohistochemistry with specific antibodies. Negative control (Control) and hematoxylin and eosin staining (H&E) are also shown. An asterisk indicates tophus deposit. Bar indicates 50 microm.. Interleukin: IL; MDP: muramyl dipeptide; LPS: lipopolysaccharide; tumor-necrosis factor: TNF; H&E: hematoxylin and eosin staining; ASC: apoptosis-associated speck-like protein containing a CARD.
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An X-ray image of her feet showed subcutaneous crystals around the first MTP joints and the overhanging margin in her right first metatarsal bone (Figure 1(a), Before, arrow). As a result, her arthritis gradually improved, subcutaneous nodules were reduced in size as determined by an X-ray image (Figure 1(a), After) and the patient's laboratory data were also improved 24 weeks after starting the treatment of tocilizumab (Table 1) (Figure 1(b)). There was no fever or acute attack during the tocilizumab treatment (Figure 1(b)). Time course of medication and plotted body temperature, serum UA (mg/dL), serum CRP (mg/dL) and serum IL-6 (pg/mL) concentrations are indicated (Figure 1(b)). TNF-alpha without any stimuli, and secreted these cytokines due to MDP (10 ng/mL or 1 microg/mL), LPS (0.1 ng/mL or 10 ng/mL) or a combination of MDP (10 ng/mL or 1 microg/mL) + LPS (0.1 ng/mL) in a dose-dependent manner (Figure 1(c)). The cytokine secretion patterns of PBMCs isolated from the patient were almost the same as those from healthy volunteers (Figure 1(c)). In her excided tophus, expression signals of cryopyrin, ASC, caspase-1, and IL-1beta were all detected in the monocytic cells and multinuclear giant cells around the MSU crystal foreign body granuloma (Figure 1(d), arrowheads).