Interleukin-17A influences the vulnerability rather than the size of established atherosclerotic plaques in apolipoprotein E-deficient mice.

Interleukin (IL)-17A plays a role in the development of atherosclerotic plaques; however, the mechanism remains unclear. In this study, apolipoprotein E-deficient (ApoE-/-) mice were fed a high-fat diet to induce atherosclerosis, followed by the treatment with exogenous recombinant IL-17A or the neutralizing antibody to confirm the impact of IL-17A on the established atherosclerotic plaques. We found that both the stimulation of IL-17A and blockage of endogenous IL-17 via antibody did not affect the size of the established plaques. However, IL-17A significantly increased the vulnerability of plaques characterized by the accumulation of lipids and T cells with a concurrent decrease in the number of smooth muscle cells. In addition, the blockage by IL-17 neutralizing antibody attenuated plaque vulnerability. Furthermore, we found that although IL-17A did not affect the efferocytosis of macrophages to apoptotic cells, it promoted the apoptosis of macrophages in the presence of oxidized low-density lipoprotein in vitro. Also, IL-17A upregulated chemokines MCP-1 and CXCL-10 expression in the plaques. Our data indicated that IL-17A controlled both SMC and macrophage accumulation and the apoptosis within the plaque, which may further weaken the aorta wall. This study suggests that IL-17A may be a potential therapeutic target for cardiovascular diseases.

Indications and effects of biological agents in the treatment of noninfectious uveitis.

Noninfectious uveitis is a common blinding eye disease, and an autoimmune response is involved in its pathogenesis. Biological agents have gradually been introduced into the treatment of noninfectious uveitis. The authors reviewed the clinical application and side effects of different biological agents on noninfectious uveitis. Biological agents that target TNF-α are widely used in the clinic. Other biological agents, such as IL-6- and IL-1-neutralizing antibodies, are used in patients who do not respond to TNF inhibitors. The efficacy of IL-17 neutralizing antibodies in noninfectious uveitis is controversial. Biological agents targeting T cells and signaling pathways provide new drug options for treatment of noninfectious uveitis. However, it cannot be ignored that these biological agents have side effects, such as increasing risk of infection.

For patients with noninfectious uveitis, if uveitis is severe and vision-threatening or if glucocorticoids and immunosuppressants are tried but do not control uveitis or cannot be used for medical reasons, biological agents offer a new choice. Many biologics are currently on the market for autoimmune diseases; some are approved for the treatment of noninfectious uveitis, and others are in clinical trials. TNF-α inhibitors are widely used in the clinic and effective in the treatment of noninfectious intermediate, posterior and pan uveitis associated with ankylosing spondylitis, Behcet's disease and juvenile idiopathic arthritis. All of these biological agents have side effects, such as increasing risk of infection or malignant tumors. Development of side effects should be closely monitored.

Inhibition of IL-17 neutralizing antibody on mice spinal cord injury and its mechanism / 国际药学研究杂志

Objective: To investigate the role of EL-17 in immune inflammatory reaction after spinal cord injury, and provide more evidence for clinical treatment of spinal cord injury on cytokine levels. Methods: Male C57B1J6 mice were randomly divided into 4 groups: in the spinal cord injury group, mice were made into spinal cord clamp model. In the sham surgery group, the dura was cut without injuring the spinal cord. Hie IL-17 neutralizing antibody group received IL-17 neutralizing antibody injection through the cadual vein at 1 h after the spinal cord clamp. Tłie solvent control group received the sterile PBS (0.01 μmol/L) through the cadual vein at 1 h after the spinal cord clamp. Mouse scale for locomotion (BMS) was applied to evaluate the mice's behavior change of hindlimb in 1-7 d. The real time fluorescent quantitative PCR was used to detect the expression changes of IL-lβ JL-6 and TNF-α mR.NA, and the immunohistochemistry technique was conducted to observe the morphological changes of neurons of NeuN on the 7th day after spinal cord injury respectivly. Results: Hie behavior score of mice after spinal cord injury indicates: the BMS scores were all 9 on the 1st to the 7th day in the sham surgery group, but were 0 on the 1st day in the model group, the IL-17 neutralizing antibody group and the solvent control group. With time extension, the motor function of hindlimhs of mice in each group were improved, but improved even better in the IL-17 neutralizing antibody group than in the model group and the solvent control group. Immunohistochemistry staining showed that after spinal cord injury, there were much complete structure of NeuN positive staining cells in the gray matter in the sham surgery group, which were obviously shrinking and protrusions disappearing in the model group and the solvent control group, while large number of NeuN neurons vacuolated and reduced significantly. It could be seen that part of neurons morphology was normal and with complete NeuN neuronal cell bodies and branches of the synapse, and the amount of NeuN neuron staining positive cells rebounded in the IL-17 neutralizing antibody group. The results of RT-qPCR on the 7th day after spinal cord injury indicated that compared with sham surgery group. IL-lβ mRNA increased significantly in the model group and the solvent control group (P<0.01); compared with the model group and the solvent control group. IL-lβ mRMA decreased significantly in the IL-17 neutralizing antibody group (P<0.05); compared with sham surgery group , TNF-α mRNA increased significantly in the model group (P<0.01); compared with the sham surgery group. TNF-α mRNA increased significantly in the solvent control group (P<0.05); compared with the model group , HVF-α mRNA decreased significantly in the IL-17 neutralizing antibody group (P< 0.05). IL-6 mRNA expression was on the decline in the IL-17 neutralizing antibody group, but without statistically significant difference with other groups. Conclusion: Combined action of IL-17. IL-lβ. EL-6 and TNF-α deteriorates the immune inflammatory of spinal cord injury, and it might relieve spinal cord injury in mice by inhibition of IL-17.

Inhibition of IL-17 neutralizing antibody on mice spinal cord injury and its mechanism / 国际药学研究杂志

Objective To investigate the role of IL-17 in immune inflammatory reaction after spinal cord injury, and provide more evidence for clinical treatment of spinal cord injury on cytokine levels. Methods Male C57BL/6 mice were randomly divided into 4 groups: in the spinal cord injury group, mice were made into spinal cord clamp model. In the sham surgery group, the dura was cut without injuring the spinal cord. The IL-17 neutralizing antibody group received IL-17 neutralizing antibody injection through the cadual vein at 1 h after the spinal cord clamp. The solvent control group received the sterile PBS (0.01 μmol/L) through the cadual vein at 1 h after the spinal cord clamp. Mouse scale for locomotion(BMS) was applied to evaluate the mice's behavior change of hindlimb in 1-7 d. The real time fluorescent quantitative PCR was used to detect the expression changes of IL-1β、IL-6 and TNF-αmRNA, and the immunohistochemistry technique was conducted to observe the morphological changes of neurons of NeuN on the 7th day after spinal cord injury respectivly. Results The behavior score of mice after spinal cord injury indicates: the BMS scores were all 9 on the 1st to the 7th day in the sham surgery group, but were 0 on the 1st day in the model group, the IL-17 neutralizing antibody group and the solvent control group. With time extension, the motor function of hindlimbs of mice in each group were improved, but improved even better in the IL-17 neutralizing antibody group than in the model group and the solvent control group. Immunohistochemistry staining showed that after spinal cord injury, there were much complete structure of NeuN positive staining cells in the gray matter in the sham surgery group, which were obviously shrinking and protrusions disappearing in the model group and the solvent control group, while large number of NeuN neurons vacuolated and reduced significantly. It could be seen that part of neurons morphology was normal and with complete NeuN neuronal cell bodies and branches of the synapse, and the amount of NeuN neuron staining positive cells rebounded in the IL-17 neutralizing antibody group. The results of RT-qPCR on the 7th day after spinal cord injury indicated that compared with sham surgery group, IL-1β mRNA increased significantly in the model group and the solvent control group(P<0.01); compared with the model group and the solvent control group, IL-1β mRMA decreased significantly in the IL-17 neutralizing antibody group(P<0.05); compared with sham surgery group , TNF-α mRNA increased significantly in the model group (P<0.01); compared with the sham surgery group, TNF-α mRNA increased significantly in the solvent control group (P<0.05); compared with the model group , TNF-α mRNA decreased significantly in the IL-17 neutralizing antibody group (P< 0.05). IL-6 mRNA expression was on the decline in the IL-17 neutralizing antibody group, but without statistically significant difference with other groups. Conclusion Combined action of IL-17, IL-1β, IL-6 and TNF-α deteriorates the immune inflammatory of spinal cord injury, and it might relieve spinal cord injury in mice by inhibition of IL-17.

Change in expression of interleukin-17 in C57 mice’s spinal cord injury area / 国际药学研究杂志

Objective: To investigate the mechanism of expression of interlenkin (IL)-17 in C57 mice’s spinal cord clamp area, and to provide new targets for clinical treatment of spinal cord injury (SCI). Methods: Male C57BL/6 mice were randomly divided into three groups. In the spinal cord injury group, mice were made into spinal cord clamp model. In the sham surgery group, the dura was cut without injuring the spinal cord. The IL-17 neutralizing antibody group received IL-17 neutralizing antibody injection through the cadual vein at 1 hour after the spinal cord clamp . Mouse scale for locomotion(BMS) was applied to evaluate the mice’s behavior change of hindlimb in 1-7 days, the real time fluorescent quantitative PCR was used to detect the change in the expression of spinal cord injury district TNF-α mRNA each time, HE staining was conducted to detect the morphological changes of spinal cord injury of the sham surgery group, the spinal cord injury group and the IL-17 neutralizing antibody group at the 7th days. Results: After spinal cord injury, the mice’s BMS score were 9 in the sham surgery group; in the model of spinal cord injury group, the mice’s BMS score were 0 on the 1st day, and 2.9 on the 7th day. In the IL-17 neutralizing antibody group, the mice’s BMS score were 0 on the 1st day, and 3.5 on the 7th day. The expression of IL-17 mRNA in the injury area peaked at the 3rd hour, which showed statistical difference when compared with sham surgery group (P0.05), and the expression of IL-17 mRNA reduced the lowest levels on the 7th day. The 7th day following spinal cord injury, mice’s spinal cord tissue was complete normal in the sham surgery group. In the spinal cord injury group, a large number of mice’s nerve cells were necrotic, a lot of cells formed vacuolated. In the IL-17 neutralizing antibody group, part of mice’s nuclear neurons were shrinking, cells formed vacuolated, but part of cells remained morphologically complete. Conclusion: IL-17 is involved in secondary immune inflammatory process of spinal cord injury, it may be targets for intervention in the treatment of spinal cord injury.

Change in expression of interleukin-17 in C57 mice′s spinal cord injury area / 国际药学研究杂志

Objective To investigate the mechanism of expression of interlenkin (IL)-17 in C57 mice′s spinal cord clamp area,and to provide new targets for clinical treatment of spinal cord injury (SCI). Methods Male C57BL/6 mice were randomly divided into three groups. In the spinal cord injury group,mice were made into spinal cord clamp model. In the sham surgery group, the dura was cut without injuring the spinal cord. The IL-17 neutralizing antibody group received IL-17 neutralizing antibody injection through the cadual vein at 1 hour after the spinal cord clamp . Mouse scale for locomotion (BMS)was applied to evaluate the mice's behavior change of hindlimb in 1-7 days,the real time fluorescent quantitative PCR was used to detect the change in the expression of spinal cord injury district TNF-αmRNA each time,HE staining was conducted to detect the morphological changes of spinal cord injury of the sham surgery group,the spinal cord injury group and the IL-17 neutralizing antibody group at the 7th days. Results After spinal cord injury,the mice's BMS score were 9 in the sham surgery group;in the model of spinal cord injury group,the mice's BMS score were 0 on the 1st day,and 2.9 on the 7th day. In the IL-17 neutralizing antibody group,the mice's BMS score were 0 on the 1st day,and 3.5 on the 7th day. The expression of IL-17 mRNA in the injury area peaked at the 3rd hour,which showed statistical difference when compared with sham surgery group (P0.05),and the expression of IL-17 mRNA reduced the lowest levels on the 7th day. The 7th day following spinal cord injury,mice's spinal cord tissue was complete normal in the sham surgery group. In the spinal cord injury group,a large number of mice's nerve cells were necrotic, a lot of cells formed vacuolated. In the IL-17 neutralizing antibody group, part of mice's nuclear neurons were shrinking, cells formed vacuolated, but part of cells remained morphologically complete. Conclusion IL-17 is involved in secondary immune inflammatory process of spinal cord injury, it may be targets for intervention in the treatment of spinal cord injury.