T-helper (Th)17 cell responses are important for the development of neutrophilic inflammatory disease. Recently, we found that acetyl salicylic acid (ASA) inhibited Th17 airway inflammation in an asthma mouse model induced by sensitization with lipopolysaccharide (LPS)-containing allergens. To investigate the mechanism(s) of the inhibitory effect of ASA on the development of Th17 airway inflammation, a neutrophilic asthma mouse model was generated by intranasal sensitization with LPS plus ovalbumin (OVA) and then challenged with OVA alone. Immunologic parameters and airway inflammation were evaluated 6 and 48 h after the last OVA challenge. ASA inhibited the production of interleukin (IL)-17 from lung T cells as well as in vitro Th17 polarization induced by IL-6. Additionally, ASA, but not salicylic acid, suppressed Th17 airway inflammation, which was associated with decreased expression of acetyl-STAT3 (downstream signaling of IL-6) in the lung. Moreover, the production of IL-6 from inflammatory cells, induced by IL-17, was abolished by treatment with ASA, whereas that induced by LPS was not. Altogether, ASA, likely via its acetyl moiety, inhibits Th17 airway inflammation by blockade of IL-6 and IL-17 positive feedback.
Animals ; Aspirin/pharmacology/*therapeutic use ; Cell Polarity/drug effects/immunology ; Feedback, Physiological/*drug effects ; Interferon-gamma/deficiency/metabolism ; Interleukin-17/*metabolism/pharmacology ; Interleukin-6/biosynthesis/*metabolism ; Lipopolysaccharides/pharmacology ; Lung/drug effects/metabolism/pathology ; Mice ; Mice, Inbred C57BL ; Pneumonia/*drug therapy/*immunology/pathology ; Th17 Cells/drug effects/*immunology/pathology ; Transforming Growth Factor beta1/pharmacology

OBJECTIVETo explore the immunoregulation existing signal transduction mechanism, to evaluate the role of lay its experimental basis By using Haoqin Qingdan decoction for treatments on the mouse models.

METHODSA total of 40 NIH Mice were randomly divided into five groups: control group, virus group (infecting by influenza virus), complex model group (richly fatty and sweet diet + Humid heat environment + infecting by influenza virus), virazole group (mouse of model group was treated by virazole), and Haoqin Qingdan decoction group (mouse of complex model group was treated by decoction of Haoqin Qingdan). When the complex model was established, determination of the mice lung indexes in each group and calculate the inhibition of lung indexes. The level of TLR2 mRNA and NF-κB mRNA expressions of peritoneal macrophages in each group of mice were quantitated by reverse transcription-polymerase chain reaction (RT-PCR). The level of IL-4 and IFN-γ in mouse serum was detected by ELISA to calculate the Th1/Th2 (IFN-γ/IL-4).

RESULTSThe lung index of control group, virus group, complex model group, virazole group and Haoqin Qingdan decoction group were separately: (0.79 ± 0.11)%, (1.93 ± 0.38)%, (1.41 ± 0.26)%, (1.10 ± 0.26)% and (1.02 ± 0.16)%; The mice of virazole group and Haoqin Qingdan decoction group lung index were decreased (t = 0.322, P < 0.05). TLR2 mRNA expression The results showed that the control group, virus group, complex model group, virazole group and Haoqin Qingdan decoction group were: 0.145 ± 0.017, 0.991 ± 0.149, 0.903 ± 0.124, 0.257 ± 0.03 and 0.413 ± 0.031; Compared to the complex model group, Haoqin Qingdan decoction group and virazole group were decreased (t = 0.422, F = 112.834, P < 0.05). Control group, virus group, complex model group, virazole group and Haoqin Qingdan decoction group NF-κB mRNA expression were separately: 0.075 ± 0.148, 0.379 ± 0.019, 0.291 ± 0.012, 0.169 ± 0.026 and 0.175 ± 0.033; the expression in virazole group and Haoqin Qingdan decoction group were decreased (t = 0.422, F = 112.834, P < 0.05). The level of IFN-γ in mice serum of control group, virus group, complex model group, virazole group and Haoqin Qingdan decoction group were: (7434.06 ± 323.27) pg/ml, (8679.77 ± 198.70) pg/ml, (8068.78 ± 113.8) pg/ml, (7454.66 ± 301.30) pg/ml and (7484.56 ± 229.85) pg/ml respectively; the IFN-γ level in serum of Haoqin Qingdan decoction group and virazole group were decreased (t = 0.201, F = 5.390, P < 0.05). Each group of mice IL-4 contents were (3701.74 ± 256.00) pg/ml, (3569.64 ± 161.35) pg/ml, (3530.88 ± 334.63) pg/ml, (3481.84 ± 282.25) pg/ml and (3618.00 ± 262.16) pg/ml; there were no significant difference between each group (t = 0.414, F = 0.505, P > 0.05). Th1/Th2 type cells in state of equilibrium (means IFN-γ/IL-4) were: 2.02 ± 0.19, 2.38 ± 0.10, 2.36 ± 0.14, 2.22 ± 0.17 and 2.07 ± 0.15; and complex model group Haoqin Qingdan decoction group and virazole group were decreased, and there was no significant difference observed (t = 0.587, F = 3.684, P > 0.05).

CONCLUSIONThe effect of Haoqin Qingdan decoction on treatment of damp-heat syndrome of pneumonia infected by influenza virus was observed. Through reducing the expressions of TLR2, it decreases the levels of NF-κB mRNA and the proportionality of Th1/Th2 are obviously descend (P < 0.05). Haoqin Qingdan decoction can reduce the lung index and relieve the pathogenic changes.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Lung ; pathology ; virology ; Male ; Mice ; Mice, Inbred Strains ; NF-kappa B ; immunology ; Orthomyxoviridae ; pathogenicity ; Phytotherapy ; Pneumonia, Viral ; drug therapy ; immunology ; virology ; Th1 Cells ; immunology ; Th2 Cells ; immunology ; Toll-Like Receptor 2 ; immunology

OBJECTIVETo analyze the safety and efficacy of anti-CD20 monoclonal antibody in treatment of severe pediatric systemic lupus erythematosus (PSLE).

METHODThe diagnosis of PSLE was made according to the criteria for the classification of systemic lupus erythematosus revised by the American College of Rheumatology in 1997. Severe cases with PSLE was selected by the following criteria: age ≤ 16 years, number of important organs involved > 1, SLEDAI score > 10 points and poor response to conventional immunosuppressive treatment. These patients received 2 doses of 375 mg/m(2) rituximab (RTX), 2 weeks apart. Clinical, laboratory findings and drug side effects were recorded at RTX initiation, 2 weeks, 1 month, 3, 6 and 12 months after infusion.

RESULTA total of 20 patients. Male to female ratio was 1:3, were enrolled. They were 5-16 years old. The course of disease was (3.0 ± 2.5) years (range: 1 month-7 years), patients were followed up for 12 - 36 months [median: (27.0 ± 7.8) months]. Delirium and cognitive disorders were significantly improved in 10 cases of lupus encephalopathy after 1 month. Lupus nephritis in children were eased slowly, 14/15 patients with lupus nephritis were improved after 2-3 months. Four cases of lupus pneumonia were significantly improved within 1 month. Decreased blood cells counts were relieved at 1 month in 16/18 cases. Cellular immune function was assessed 2 weeks after application of anti-CD20 monoclonal antibody; we found B-cell clearance in 19 patients (95%). B lymphocyte count of 18 patients (90%) was restored within one year. SLEDAI score was reduced obviously. Dose of corticosteroid ranged from (45.0 ± 4.7) mg/m(2) before drug use to (12.0 ± 2.7) mg/m(2) 12 months later (P < 0.001). After the drug use, 5 patients had pneumonia within 6 months; 2 cases who suffered from aspergillus pneumonia and Pneumocystis carinii pneumonia respectively were severe. They accepted mechanical ventilation and anti-inflammatory support after being transferred to the intensive care unit, and their conditions improved at last. No death occurred. In 2 patients the disease recurred with B-cell recovery after 15 months and 18 months. Administration of another cycle of rituximab resulted in remission again in one case but not in the other.

CONCLUSIONAnti-CD20 monoclonal antibody is effective and safe in treatment of severe PSLE. But severe infections may occur in some cases. Focusing on prevention and early treatment can reduce the probability of adverse reactions.

Adolescent ; Antibodies, Monoclonal, Murine-Derived ; administration & dosage ; adverse effects ; therapeutic use ; B-Lymphocytes ; drug effects ; immunology ; Biomarkers ; blood ; Child ; Child, Preschool ; Cyclophosphamide ; administration & dosage ; Female ; Follow-Up Studies ; Glucocorticoids ; administration & dosage ; therapeutic use ; Humans ; Immunologic Factors ; administration & dosage ; adverse effects ; therapeutic use ; Lupus Erythematosus, Systemic ; complications ; drug therapy ; immunology ; Lupus Nephritis ; etiology ; pathology ; Male ; Pneumonia ; etiology ; pathology ; Prednisolone ; administration & dosage ; therapeutic use ; Rituximab ; Severity of Illness Index ; Treatment Outcome