BACKGROUND: Iguratimod is a new type of disease modifying anti-rheumatic drug, which reduced the production of inflammatory cytokines. The purpose of this study was to evaluate pharmacokinetic characteristics and safety profiles of iguratimod after a single oral administration in healthy Korean volunteers. METHODS: A randomized, double-blind, placebo-controlled, parallel group, single oral dose study was conducted in 24 healthy male volunteers. Three groups of eight subjects each received 25 mg, 50 mg, or 100 mg dosage, respectively. Two subjects in each dose group were administered matching placebo. Plasma concentrations of iguratimod were measured till 72 hours after drug administration. Tolerability was evaluated by monitoring adverse events, clinical laboratory tests, and 12-lead electrocardiograms. RESULTS: The mean area under the concentration-time curve from 0 to 72 hours (AUClast) were 11.9, 25.2, and 51.8 mg x h/L and the maximum plasma concentration (Cmax) were 1.15, 2.33, and 4.78 mg/L in 25, 50 and 100 mg dose groups, respectively. All doses of iguratimod were well tolerated without serious adverse events or clinically meaningful changes. CONCLUSION: Cmax and AUClast values of iguratimod proportionally increased with incremental dose. Iguratimod was generally safe and well tolerated.
Administration, Oral* ; Cytokines ; Electrocardiography ; Humans ; Male ; Pharmacokinetics* ; Plasma

Tissue engineering has been applied to various tissues, and particularly significant progress has been made in the areas of skin, cartilage, and bone regeneration. Inclusion of bioactive factors into the synthetic scaffolds has been suggested as one of the possible tissue engineering strategies. The growth factors are polypeptides that transmit signals to modulate cellular activities. They have short half-lives, for example, platelet-derived growth factor (PDGF), isolated from platelets, has a half life of less than 2 minutes when injected intravenously. Extended biological activity and the controlled release of growth factor are achieved by incorporating growth factor into the polymeric device. This review will focus on growth factor delivery for tissue engineering. Particular examples will be given whereby growth factors are delivered from a tissue-engineered device to facilitate wound healing and tissue repair.
Animal ; Biomedical Engineering/methods* ; Bone Morphogenetic Proteins/administration & dosage ; Cytokines/therapeutic use ; Cytokines/administration & dosage* ; Growth Substances/physiology

No abstract available.
Anti-Inflammatory Agents/*administration & dosage ; Cytokines/blood ; Diphosphonates/*administration & dosage ; Humans ; Injections, Intravenous ; Osteoporosis/*drug therapy

OBJECTIVETo detect the number of cells and the level of IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN-γ and IL-17 cytokines in the peripheral blood of mice exposed to rocket kerosene by skin.

METHODICR mice were randomly divided into the normal control group and RK experimental group (400 µl×1 group). RK undiluted fuel were applied directly to the dorsal skin of the mice. In control groups were treated with sesame oil (SO). the number of blood cells were detected by automatic blood cell counter and the level of IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN-γ and IL-17 cytokines in serum were detected by using flow cytometry and BD CBA Flex set kit.

RESULTCompared with the normal group, WBC and LYM had a decreasing tendency 2 h and decreased significantly 6 h, 12 h and 1 d after RK exposure (P<0.05). They increased significantly 7 d after RK exposure (P<0.05). Compared with the normal group, the level of IL-6 increased significantly 2 h, 6 h, 12 h,1 d and 3 d (P<0.05). The level of TNF-α increased significantly 2h, 3d, 5d and 7d (P<0.05). The level of IL-10 increased significantly 2 h, 6 h, 3 d, 5 d and 7 d (P<0.05). The level of IFN-γ increased significantly 6 h and 3 d (P< 0.05). The level of IL-17 significantly increased 3 d, 5 d and 7d (P<0.05).

CONCLUSIONRK can change the number of immune cells, causing the immune cytokine changes in mice after RK cutaneous exposure.

Administration, Cutaneous ; Animals ; Blood Cell Count ; Cytokines ; blood ; Flow Cytometry ; Kerosene ; toxicity ; Mice ; Mice, Inbred ICR

Silk peptide, the hydrolysate of silk protein derived from cocoons, has been employed as a biomedical material and is believed to be safe for human use. Silk peptide display various bioactivities, including anti-inflammatory, immune-regulatory, anti-tumor, anti-viral, and anti-bacterial. Although earlier investigations demonstrated that silk peptide stimulates macrophages and the production of pro-inflammatory cytokines, its effect on natural killer (NK) cell function has not yet been explored. In this study, we initially confirmed that silk peptide enhances NK cell activity in vitro and ex vivo. To assess the modulatory activity of silk peptide on NK cells, mice were fed various amounts of a silk peptide-supplemented diet for 2 months and the effects on immune stimulation, including NK cell activation, were evaluated. Oral administration of silk peptide significantly enhanced the proliferation of mitogen- or IL-2-stimulated splenocytes. In addition, oral silk peptide treatment enhanced the frequency and degree of maturation of NK cells in splenocytes. The same treatment also significantly enhanced the target cell cytolytic activity of NK cells, which was determined by cell surface CD107a expression and intracellular interferon-γ expression. Finally, oral administration of silk peptide stimulated T helper 1-type cytokine expression from splenic lymphocytes. Collectively, our results suggest that silk peptide potentiates NK cell activity in vivo and could be used as a compound for immune-modulating anti-tumor treatment.
Administration, Oral* ; Animals ; Cytokines ; Diet ; Humans ; In Vitro Techniques ; Killer Cells, Natural* ; Lymphocytes ; Macrophages ; Mice ; Silk*

BACKGROUND/AIMS: Ulcerative colitis (UC) is a chronic disease that characteristically has a relapsing and remitting course. Probiotics might possibly induce remission in the treatment of active UC. Aims of our study were to assess the efficacy of VSL#3 on clinical response and colonic tissue cytokine concentration changes in patients with active UC. METHODS: Twenty-four eligible patients with mild to moderate UC received open-label VSL#3 4 sachets daily in 2 divided doses for 8 weeks. The disease activity pre- and post-VSL#3 therapy was assessed by ulcerative colitis disease activity score and colonic tissue cytokine profiling done at baseline and at week 8. RESULTS: Twenty-four patients (mean age, 43.7 years; range, 20-70 years; male/female, 15/9) were enrolled and 2 patients did not have the final endoscopic assessment. A total of 22 patients were analyzed. Intent to treat analysis demonstrated remission in 45.8% of subjects (n=11); partial response in 20.8% (n=5); no change or worse in 25.0% (n=6) of subjects. The mean ulcerative colitis disease activity index (UCDAI) scores decreased from 7.09+/-1.81 to 1.45+/-1.29 in patients with a remission (p<0.001). The mean endoscopic scores had also significantly decreased from 1.91+/-0.54 to 0.63+/-0.50 in patients with a remission (p<0.001). The concentrations of colonic cytokines did not change significantly during treatment in patients with a remission. CONCLUSIONS: Our study demonstrated that VSL#3 is effective in achieving clinical responses and remissions in patients with mild-to moderately active UC, further supporting the potential role in UC therapy.
Adult ; Aged ; Colitis, Ulcerative/*therapy ; Cytokines/metabolism ; Drug Administration Schedule ; Humans ; Male ; Middle Aged ; Probiotics/*therapeutic use ; Severity of Illness Index

PURPOSE: We wanted to evaluate the changes of the expression of macrophage migration inhibitory factor(MIF) according to time, so we determined the semiquantitative score from immunostaining in a bladder inflammatory rat model. MATERIALS AND METHODS: A total of 25 female Sprague-Dawley rats were divided into 5 groups according to the time course. Group 1 was the control group that was treated with an intravesical instillation of saline. Groups 2-5 were evaluated at 4 hours, 24 hours, 48 hours and 7 days after the instillation of lipopolysaccharide(LPS), respectively. H&E staining and immunohistochemical staining for MIF were performed after removing the bladder. A semiquantitative score was used to evaluate the cystitis(bladder inflammation score; BIS). The expression of MIF in the bladder was graded from 0 to 3+(MIF score; MIFS). RESULTS: The staining of MIF was the most intense in the basal layer of the urothelium in the control group(BIS 0, MIFS 3). The degree of bladder inflammation was highest in group 3, and MIF was not expressed even in the urotherlium without inflammation(BIS 2.2, MIFS 0.6). The bladder inflammation was decreased after 48 hours, and the expression of MIF was increased after 48 hous(BIS 1.7, MIFS 1.6). The severity of bladder inflammation and the expression of MIS were significantly changed with the time course(p<0.001). CONCLUSIONS: These results suggest that pre-formed MIF is stored in the cytoplasm of the basal cells in the urothelium, and it is released into the lumen of the bladder after a noxious stimulus like LPS.
Administration, Intravesical ; Animals ; Cystitis* ; Cytokines ; Cytoplasm ; Female ; Humans ; Inflammation ; Lipopolysaccharides ; Macrophages* ; Models, Animal ; Rats* ; Rats, Sprague-Dawley ; Urinary Bladder ; Urothelium

PURPOSE: In this prospective study, we evaluated the clinical significance of inflammatory cytokines in women with acute uncomplicated pyelonephritis undergoing antimicrobial therapy. MATERIALS AND METHODS: We analyzed 26 female patients diagnosed with acute uncomplicated pyelonephritis between September 2007 and March 2008. Body temperature, white blood cell (WBC) counts, serum C-reactive protein (CRP), and serum and urine interleukin (IL)-6 and IL-8 were measured before and 12 hours, 24 hours, and 4 days after the intravenous administration of empirical ciprofloxacin. RESULTS: Initial serum CRP levels were correlated with initial serum IL-6 and initial urine IL-8 levels. Twenty-four hours after the start of antibiotic treatment, the CRP level and urine IL-8 level continued to be high, whereas serum IL-6 levels decreased significantly (26.1+/-32.4 vs 9.9+/-23.5pg/dl, p<0.01). When we divided the patients into mild (CRP<15mg/dl, n=14) and severe (CRP> or =15mg/dl, n=12) groups according to initial CRP levels, the serum IL-6 level decreased significantly in both the mild (14.2+/-4.0 vs 4.0+/-1.7pg/dl, p<0.01) and the severe (41.1+/-12.7 vs. 22.7+/-16.4pg/dl, p<0.01) groups within 24 hours, whereas CRP and urine IL-8 levels did not change significantly in either group. CONCLUSIONS: Clinically, initial serum IL-6 and urine IL-8 levels were increased according to disease severity. Moreover, the serum IL-6 level decreased rapidly after antibiotic treatment within 24 hours. Serum IL-6 levels are a better indicator of the severity of disease and the therapeutic effect of empirical parenteral antibiotic use in patients with acute uncomplicated pyelonephritis than were either CRP or WBC counts.
Administration, Intravenous ; Body Temperature ; C-Reactive Protein ; Ciprofloxacin ; Cytokines ; Female ; Humans ; Interleukin-6 ; Interleukin-8 ; Interleukins ; Leukocytes ; Prospective Studies ; Pyelonephritis

OBJECTIVETo study the alteration of thymus matrix lymphocyte generator (TSLP) and change of the Th factor in the course of disease development, and to analyze the curative effect of inhalation of Vitamin A (VA) with corticosteroid for the treatment of asthmatic pneumonia.

METHODSAsthmatic pneumonia models were prepared by challenging rats with inhalation of ovalbumin for 4 weeks, and rested for 1 week. The treatment with VA and corticosteroid inhalation for 1 week was followed. The rat thymus and lung specimen were examen by histochemical and immunofluorescence staining.

RESULTSAfter 4 - 5 weeks of stimulation, there were more TSLP-positive cells and alveolar macrophages (AM) found in thymus and lung tissue of asthmatic group, the cell proliferation in spleen and thymus was obvious, and blood Th factors elevated. The inflammation within the lung tissue aggravated gradually. In VA group, the expression of TSLP and Th2 factors were all lowered at the 4th week. The TSLP expression slightly increased at the 5th week, and the cell proliferation within T-cell zone of spleen and thymus was strong at first and weakened later. Alveolar microphages (AM) increased significantly and the inflammation in the lung subsided gradually at the 5th week. In the hormone group, TSLP and Th2 factors expression in both thymus and lung were decreased at the 5th week, while the cell proliferation in thymus and lung was gradually increased. The quantity of AM was decreased, whereas the inflammation of the lung was increased gradually at the 5th week.

CONCLUSIONDuring asthmatic period elevated TSLP expression was accompanied by Th2 type responses while VA and corticosteroid both suppressed TSLP and Th2 factors expression. VA alone promoted T lymphocyte proliferation as well as the antigen elimination function by AM, after ceasing the usage, the lung inflammation abated gradually. In contrast, after ceasing the use of corticosteroid, inflammation aggravated.

Administration, Inhalation ; Adrenal Cortex Hormones ; administration & dosage ; therapeutic use ; Animals ; Asthma ; complications ; Beclomethasone ; administration & dosage ; therapeutic use ; Cytokines ; metabolism ; Pneumonia ; drug therapy ; metabolism ; Rats ; Rats, Sprague-Dawley ; Vitamin A ; administration & dosage ; therapeutic use

OBJECTIVETo investigate the mechanism of action on compatible using of total alkaloids of Radix Aconiti Praeparata and total glycosides or polysaccharides of Radix Paeoniae Alba therapy on rheumatoid arthritis in rats.

METHODThe rat models of rheumatoid arthritis of cold and dampness syndrome were treated with total alkaloids of Radix Aconiti Praeparata and total glycosides or polysaccharides of Radix Paeoniae Alba. Observed the contents of hypothalamic L-ENK, hypothalamic-END, plasmatic SP, serumal IgG, serumal cell factors (IL-1beta, TNF-alpha, IL-6, IL-2, IL-10) by radioimmunity method and ultrastructural change of synovial cell in electron microscope.

RESULTTotal alkaloids of Radix Aconiti Praeparata and total glycosides or polysaccharides of Radix Paeoniae Alba could relieve arthrocele and arthralgia and elevate the contents of L-ENK, beta-END, IL-2 and degrade the contents of SP, IgG, IL-1beta, IL-6 and inhibit abnormal secretion accentuation of synovial cell like fiber.

CONCLUSIONTotal alkaloids of Radix Aconiti Praeparata and total glycosides or polysaccharides of Radix Paeoniae Alba could be used to treat rheumatoid arthritis of cold and dampness syndrome. The mechanism of action might be that the contents of center endogenous opioid peptides had increased, the synthesis and release of SP had been inhibited, the disturbance of serumal cell factor had been adjusted, and the synthesis and secretion of serum immune globulin and abnormal secretion accentuation of synovial cell had been inhibited.

Aconitum ; chemistry ; Alkaloids ; administration & dosage ; Animals ; Arthritis, Rheumatoid ; drug therapy ; genetics ; immunology ; Cytokines ; genetics ; immunology ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Glycosides ; administration & dosage ; Humans ; Male ; Paeonia ; chemistry ; Polysaccharides ; administration & dosage ; Rats ; Rats, Sprague-Dawley