Airway remodeling in asthma is a result of persistent inflammation and epithelial damage in response to repetitive injury. Recent studies have identified several important mediators associated with airway remodeling in asthma, including transforming growth factor-beta, interleukin (IL)-5, basic fibroblast growth factor, vascular endothelial growth factor, LIGHT, tumor necrosis factor (TNF)-alpha, thymic stromal lymphopoietin, IL-33, and IL-25. In addition, the epithelium mesenchymal transformation (EMT) induced by environmental factors may play an important role in initiating this process. Diagnostic methods using sputum and blood biomarkers as well as radiological interventions have been developed to distinguish between asthma sub-phenotypes. Human clinical trials have been conducted to evaluate biological therapies that target individual inflammatory cells or mediators including anti IgE, anti IL-5, and anti TNF-alpha. Furthermore, new drugs such as c-kit/platelet-derived growth factor receptor kinase inhibitors, endothelin-1 receptor antagonists, calcium channel inhibitors, and HMG-CoA reductase inhibitors have been developed to treat asthma-related symptoms. In addition to targeting specific inflammatory cells or mediators, preventing the initiation of EMT may be important for targeted treatment. Interestingly, bronchial thermoplasty reduces smooth muscle mass in patients with severe asthma and improves asthma-specific quality of life, particularly by reducing severe exacerbation and healthcare use. A wide range of different therapeutic approaches has been developed to address the immunological processes of asthma and to treat this complex chronic illness. An important future direction may be to investigate the role of mediators involved in the development of airway remodeling to enhance asthma therapy.
Airway Resistance/*immunology ; Asthma/immunology/*pathology/therapy ; Biological Therapy ; Cytokines ; Eosinophils ; Epithelium ; Humans ; Inflammation/immunology/*pathology/therapy ; Interleukin-5 ; Tumor Necrosis Factor-alpha

OBJECTIVETo probe the recovery mechanism of Zhenggu powder (ZGP) on acute soft tissue injury in cell levels.

METHODSForty rabbits which established animal model of acute soft tissue injury with hammer hitting,were divided randomly into normal group (A), model group (B), vaseline group (C)and ZGP group (D). Injured part was applied external drug daily after model was made. All animals were killed after using drug for 4 days. The local tissue of injured part was taken pathologic study, and was measured the content of IL-1beta, IL-6, TNFalpha by ELISA method and TXB2, 6-keto-PGF1alpha by RIA method.

RESULTSMuscular tissue of group A was normal. But that of group B and C was aberrant,such as swelling and broken of muscular fiber or infiltration of inflammatory cell. Such histological change of group D was lightly and hyperplasia of blood vessel was found. The contents of IL-1beta, TNFalpha, TXB2 and TXB2/6-keto-PGF1alpha in group D were lower than that of group B and group C. On the contrary, the contents of 6-keto-PGF1alpha in the group D were higher than that of group B and group C. The difference of content of IL-6 between groups was not obvious.

CONCLUSIONZGP could promote not only the dilution and the transportation of inflammatory cell factors,but also the repair and the regeneration of the injured tissue structures. The therapeutic effect of ZGP was not relative to IL-6.

Animals ; Cytokines ; immunology ; Drugs, Chinese Herbal ; pharmacology ; Female ; Humans ; Inflammation Mediators ; immunology ; Male ; Rabbits ; Random Allocation ; Soft Tissue Injuries ; drug therapy ; immunology ; pathology

We evaluated the inflammatory indices according to the fever duration in children with Kawasaki disease (KD), and determined duration when the inflammatory processes in KD reach their peak. Children with KD (n=152) were classified into 7 groups according to fever duration: at the third day or earlier (n=20), fourth (n=33), fifth (n=46), sixth (n=15), seventh (n=15), eighth (n=9), and at the ninth day or later after fever onset (n= 14). The levels of various laboratory indices were determined 3 times: before, 24 hr and 7 days after intravenous immunoglobulin administration (2 g/kg). WBC and neutrophil counts, and C-reactive protein level were the highest at the sixth day. Levels of hemoglobin, albumin, and high density lipoprotein cholestrol were the lowest at the sixth day. Although these indices were not significant statistically between groups, the indices showed either bell-shaped or U-shaped distribution of which peak or trench were at the sixth day. These findiugs showed that the inflammatory processes in KD reach peak on the sixth day of fever onset. This finding is important because a higher single-dose intravenous immunoglobulin treatment before the peak day may help reduce the coronary artery lesions in KD.
Child, Preschool ; Coronary Vessels/pathology ; Female ; *Fever/blood ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Infant ; *Inflammation/blood/immunology ; Male ; *Mucocutaneous Lymph Node Syndrome/blood/immunology/pathology/therapy ; Time Factors

Nonalcoholic steatohepatitis (NASH) can progress into liver cirrhosis; however, no definite treatment is available. Omega-3 polyunsaturated fatty acid (omega-3) has been reported to alleviate experimental NASH, although its beneficial effect was not evident when tested clinically. Thus, this study aimed to investigate the additive effect of omega-3 and ursodeoxycholic acid (UDCA) on diet-induced NASH in mice. C57BL/6 mice were given a high-fat diet (HFD) for 24 weeks, at which point the mice were divided into three groups and fed HFD alone, HFD with omega-3 or HFD with omega-3 in combination with UDCA for another 24 weeks. Feeding mice an HFD and administering omega-3 improved histologically assessed liver fibrosis, and UDCA in combination with omega-3 further attenuated this disease. The assessment of collagen alpha1(I) expression agreed with the histological evaluation. Omega-3 in combination with UDCA resulted in a significant attenuation of inflammation whereas administering omega-3 alone failed to improve histologically assessed liver inflammation. Quantitative analysis of tumor necrosis factor alpha showed an additive effect of omega-3 and UDCA on liver inflammation. HFD-induced hepatic triglyceride accumulation was attenuated by omega-3 and adding UDCA accentuated this effect. In accordance with this result, the expression of sterol regulatory binding protein-1c decreased after omega-3 administration and adding UDCA further diminished SREBP-1c expression. The expression of inducible nitric oxide synthase (iNOS), which may reflect oxidative stress-induced tissue damage, was suppressed by omega-3 administration and adding UDCA further attenuated iNOS expression. These results demonstrated an additive effect of omega-3 and UDCA for alleviating fibrosis, inflammation and steatosis in diet-induced NASH.
Animals ; Cholagogues and Choleretics/pharmacology/*therapeutic use ; Diet, High-Fat/adverse effects ; Drug Synergism ; Fatty Acids, Omega-3/pharmacology/*therapeutic use ; Fibrosis/drug therapy/etiology/immunology/pathology ; Inflammation/drug therapy/etiology/immunology/pathology ; Liver/*drug effects/immunology/pathology ; Male ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/*drug therapy/etiology/immunology/pathology ; Ursodeoxycholic Acid/pharmacology/*therapeutic use

Nonspecific inflammatory response is the major cause for failure of islet grafts at the early phase of intraportal islet transplantation (IPIT). Bilirubin, a natural product of heme catabolism, has displayed anti-oxidative and anti-inflammatory activities. The present study has demonstrated that bilirubin protected islet grafts by inhibiting nonspecific inflammatory response in a syngeneic rat model of IPIT. The inflammation-induced cell injury was mimicked by exposing cultured rat insulinoma INS-1 cells to cytokines (IL-1beta, TNF-alpha and IFN-gamma) in in vitro assays. At appropriate lower concentrations, bilirubin significantly attenuated the reduced cell viability and enhanced cell apoptosis induced by cytokines, and protected the insulin secretory function of INS-1 cells. Diabetic inbred male Lewis rats induced by streptozotocin underwent IPIT at different islet equivalents (IEQs) (optimal dose of 1000, and suboptimal doses of 750 or 500), and bilirubin was administered to the recipients every 12 h, starting from one day before transplantation until 5 days after transplantation. Administration of bilirubin improved glucose control and enhanced glucose tolerance in diabetic recipients, and reduced the serum levels of inflammatory mediators including IL-1beta, TNF-alpha, soluble intercellular adhesion molecule 1, monocyte chemoattractant protein-1 and NO, and inhibited the infiltration of Kupffer cells into the islet grafts, and restored insulin-producing ability of transplanted islets.
Animals ; Apoptosis/drug effects/immunology ; Bilirubin/*administration & dosage/pharmacology ; Cell Line, Tumor ; Cytokines/immunology/metabolism ; Diabetes Mellitus, Experimental/*drug therapy/*immunology ; Inflammation ; Inflammation Mediators/immunology/metabolism ; Islets of Langerhans/drug effects/*immunology/injuries/pathology ; *Islets of Langerhans Transplantation ; Male ; Oxidative Stress/drug effects/immunology ; Rats ; Rats, Inbred Lew ; Transplantation, I

OBJECTIVETo investigate the effect of prostaglandin D2 receptor antagonists on the airway inflammation in rats with asthma.

METHODSForty male SD rats were randomly divided into four groups: Group A (normal control), Group B (asthma group), Group C (CRTH2 antagonist BAYu3405 treatment group), Group D (DP1 antagonist BWA868C treatment group). Asthma was induced by ovalbumin (OVA) challenge. The rats in each group were sacrificed 24 h after the last challenge of OVA.DP1/CRTH2 receptors on eosinophils (EOS) were measured by radiological binding assay (RBA). The left lungs were used for histological examinations and bronchoalveolar lavage fluid (BALF) was collected from the right lungs. The total cell numbers, EOS absolute count and differential cell counts in BALF were performed. Serum concentrations of IL-4, 5 and IFN-gamma were measured by ELISA.

RESULTSRats in BAYu3405 treatment group showed profoundly decreased infiltrates of EOS and lymphocytes in the wall of bronchus when compared with those of asthma group and BWA868C treatment group. Serum concentrations of IFN-gamma in rats of BAYu3405 treatment group increased, but IL-4 and IL-5 decreased significantly when compared with those in rats of asthma group and BWA868C treatment group (P<0.01), and BALF EOS count was decreased significantly (P<0.01). Peripheral blood EOS count was higher than that in rats of normal control group, but was not significantly different from that in rats of asthma group and BWA868C treatment group. The combining capacity of CRTH2 and DP total combining capacity on EOS in asthma group, BAYu3405 treatment group and BWA868C treatment group were significantly higher than those in Group A (P<0.01). There was no significant difference in DP1 among all the groups (P>0.05).

CONCLUSIONCRTH2, but not DP1 antagonist can effectively ameliorate airway inflammation in rats with asthma.

Animals ; Asthma ; chemically induced ; drug therapy ; pathology ; Bronchi ; immunology ; pathology ; Carbazoles ; pharmacology ; therapeutic use ; Inflammation ; drug therapy ; Male ; Ovalbumin ; Prostaglandin D2 ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Immunologic ; antagonists & inhibitors ; Receptors, Prostaglandin ; antagonists & inhibitors ; Sulfonamides ; pharmacology ; therapeutic use

Animals ; Asthma ; drug therapy ; immunology ; pathology ; Cyclohexanecarboxylic Acids ; therapeutic use ; Cytokines ; physiology ; Eosinophils ; physiology ; Genetic Therapy ; Humans ; Inflammation ; pathology ; Matrix Metalloproteinase 2 ; physiology ; Matrix Metalloproteinase 9 ; physiology ; Nitriles ; Quinolines ; therapeutic use ; Signal Transduction

OBJECTIVETo observe the efficacy of ursodeoxycholic acid (UDCA) combined with Tongdan: Decoction () on immunological indices and histopathological changes in patients with primary biliary cirrhosis (PBC) of IIor III histological stage.

METHODSSixty PBC patients were assigned randomly and equally: to the control group treated with UDCA alone and the treatment group treated with UDCA combined with Tongdan Decoction. The immunological indices and histopathological changes were detected before and after 24-week treatment, and the follow-up lasted for 1-3 years.

RESULTSAfter 24-week treatment, CD4(+)CD28(-) in the peripheral blood was lowered and CD4(+)CD25(+) was increased in both groups, and better effect was shown in the treatment group (P<0.01). The levels of IgM, IgG, and IgA decreased markedly after 96-week treatment in the treatment group (P< 0.05, P< 0.01), while in the control group, only the latter two showed significant decrease after 148 week (all P<0.05). At the end of the 3-year follow-up, the medians of histopathological <inflammation grading and fibrosis staging declined to a lower rank, and the effect on inflammation was superior in the treatment group to the control group shown by non-parameters Wilcoxon paired symbols test ( Z=2.761,P=0.006).

CONCLUSIONCombined therapy of Tongdan Decoction and UDCA showed a better therapeutic effect: than UDCA monotherapy on PBC, especially in improving immunological indices and histopathological hepatic changes.

Antigens, CD ; blood ; Biomarkers ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Immunoglobulin G ; blood ; Inflammation ; blood ; complications ; Liver Cirrhosis, Biliary ; blood ; drug therapy ; immunology ; pathology ; Male ; Middle Aged ; Ursodeoxycholic Acid ; therapeutic use

Endothelin (ET) receptor antagonists have been developed to produce a reduction of ET related effects in various diseases, as well as in animal models of airway inflammation. We aimed to investigate the anti-inflammatory potential of bosentan on a rat model of emphysema. Thirty Wistar male rats were classified as control group (group 1), intratracheally (i.t.) instilled with saline, treated with vehicle solution; elastase group (group 2), i.t. instilled with porcine pancreatic elastase (PPE), treated with vehicle solution; and PPE+bosentan group (group 3), i.t. instilled with PPE, treated with bosentan. The levels of TNF-alpha, IL-1beta, IL-6, and IL-8 in bronchoalveolar lavage fluid (BALF) and lung tissue, cell counts in BALF, and histologic analysis of all groups were evaluated. Neutrophile granulocytes (NG) and alveolar macrophages (AM) were increased more in group 2 than in group 1 (P<0.001, P=0.04, respectively). Compared with group 2, neutrophil granulocyte (NG) and alveolar macrophages (AM) counts were decreased in group 3 (P< 0.001). Histological examination confirmed a diffuse neutrophilic inflammation and irregular alveolar air space enlargement in group 2. Treatment with bosentan partially reduced the enlarged lung volumes. Compared with group 1, the BALF levels of TNF-alpha and IL-6, and the lung tissue levels of IL-1beta, IL-6, and IL-8 were increased in group 2 (P=0.028, P=0.005, P=0.001, P=0.019, P<0.001, respectively). The TNF-alpha and IL-8 levels of BALF (P=0.007, P=0.001, respectively), and the TNF-alpha, IL-1beta, IL-6, and the IL-8 levels of lung tissue (P=0.031, P=0.017, P=0.007, P<0.001) were decreased in group 3 compared to group 2. In conclusion, bosentan decreased the inflammatory response by reducing numbers of inflammatory cells and proinflammatory cytokines.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Bronchoalveolar Lavage Fluid/cytology/immunology ; Cytokines/*biosynthesis ; Disease Models, Animal ; Emphysema/*drug therapy/etiology/immunology/pathology ; Inflammation Mediators/metabolism ; Lung/drug effects/immunology/pathology ; Male ; Pancreatic Elastase/administration & dosage/toxicity ; Rats ; Rats, Wistar ; Receptors, Endothelin/*antagonists & inhibitors ; Sulfonamides/*pharmacology

OBJECTIVETo study the influence of Yanyankang powder on Th1/Th2 in rats with experimental autoimmune uveitis (EAU).

METHODSThe EAU models were induced in Lewis rats by immunization with interphotoreceptor retinoid binding protein (IRBP) 1177-1191 in complete Freund's adjuvant. The rats were randomly divided into 3 groups: a model control group, a Yanyankang group, and a prednisone group, 9 rats in each group. The model control group was intervened with saline solution by gavage. The Yanyankang group was intervened with Yanyankang powder 4 g/(kg day) by gavage. The prednisone group were intervened with prednisone acetate tablets 5 mg/(kg d) by gavage. All groups were intervened after immunization once every 2 days for 18 days and monitored by slit-lamp biomicroscopy daily until day 18. The levels of gamma interferon (INF-γ) and interleukin-10 (IL-10) in the supernatants of T cells were determined by enzyme-linked immunosorbent assay. Polymerase chain reaction (PCR) technology was used for measuring Th1 and Th2 related cytokine mRNA expressions.

RESULTSSlighter intraocular inflammation was found in the Yanyankang group and the prednisone group than the control group. The levels of the IFN-γ and IL-10 in the supernatants of the spleen lymph node cells were 382.33±6.30, 155.87±4.46 μg/L in the Yanyankang group and 270.93±7.76, 265.32±11.88 μg/L in the prednisone group. Both had significant differences compared with the control group (941.53±8.59, 20.67±4.65 μg/L; =0.01). The PCR results showed the same tendency.

CONCLUSIONYanyankang powder showed favorable effects in the rats with EAU by influencing the function of Th1 and Th2 cells.

Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Eye ; pathology ; Female ; Immunization ; Inflammation ; pathology ; Interferon-gamma ; genetics ; metabolism ; Interleukin-10 ; genetics ; metabolism ; Lymph Nodes ; drug effects ; metabolism ; Powders ; RNA, Messenger ; genetics ; metabolism ; Rats, Inbred Lew ; Spleen ; metabolism ; Th1 Cells ; drug effects ; immunology ; Th2 Cells ; drug effects ; immunology ; Uveitis ; drug therapy ; genetics ; immunology