Aim To investigate the effects of predni-sone on trabecular microstructure and biomechanical properties of femur in a rat model of type II collagen-induced arthritis (CIA ) using micro-CT and biome-chanics.Methods Forty 8-week-old male Lewis rats were randomly divided into 2 groups:control (CON ) group with 6 rats,and the remaining 34 rats were used to establish the CIA model.3 weeks after immunization screening CIA rats were randomly divided into CIA group,CIA plus prednisone 4.5 mg · kg-1 · d -1 group and CIA plus prednisone 9 mg · kg-1 · d -1 group.Rats in CON group were given vehicle as well as in CIA group.Rats in the other two groups were treated with prednisone at 4.5 mg·kg-1 ·d -1 or 9 mg ·kg-1 · d -1 .After 90 days treatment,all rats were euthanized,and the left femur was collected for biome-chanics,micro-CT scanning and three-dimensional re-construction.Results Micro-CT data showed that tra-becular thickness,trabecular number,bone volume/total volume,bone mineral density in CIA group were significantly lower than those in CON group.While tra-becular separation,structure model index were signifi-cantly higher than those in CON group.Compared with CON group,biomechanical properties (elastic load, maximum load,break load and stiffness)were signifi-cantly decreased in CIA group.Compared with CIA group,bone volume/total volume and trabecular num-ber were increased,while trabecular separation was significantly decreased in two prednisone groups.Com-pared with CIA group,there was no significant change in biomechanical properties in two prednisone groups. Conclusions Treatment with prednisone for 3 months can ameliorate the damage of trabecular microstructure of the femur in CIA rats,but it has no effect on biome-chanical properties and bone mineral density.

Objectives To identify the effects of tuberculin purified protein derivative (PPD) sensitization on attenuating pulmonary T helper 2 (Th2) reaction and eosinophil infiltration in ovalbumin sensitized mice, and to search for the possibility of its clinical use in the management of asthma in a new way.Methods　Sixty C57BL/6 mice were sensitized with PPD and then with ovalbumin and aluminum hydroxide, and randomized into 4 groups: ovalbumin (OVA), pre-PPD, post-PPD and control groups. Aerosol PPD were administered 3 h before or after ovalbumin challenge in the pre-PPD and post-PPD groups respectively, and control group received aerosol PPD only. IL-4, IL-5 expression was detected by immunocytochemistry in situ hybridization. Lung slides were stained with eosin and hemotoxylin, and pathological changes were observed.Results　Ovalbumin aerosol inhalation caused a mixed inflammatory infiltration dominated by CD4+ T lymphocytes and eosinophils in the lung of sensitized mice. 87.5%-89.7% and 89.0%-89.2% of the CD4+ T lymphocytes were IL-4 mRNA+ and IL-5 mRNA+ respectively. 88.7%-91.2% of IL-4 mRNA+ cells and 89.8%-90.6% of IL-5 mRNA+ cells were CD4+ T lymphocytes in OVA group. Aerosol administration of PPD markedly suppressed IL-4 and IL-5 expression, and lung eosinophil infiltration. It was more effective in pre-PPD group. 76.6%-78.0% of IL-4 mRNA+ and 73.8%-79.7% of IL-5 mRNA+ cells were CD4+ and 78.1%-84.9% and 78.4%-85.3% of the CD4+ cells were IL-4 mRNA+ or IL-5 mRNA+ respectively in pre-PPD group, both were markedly lower than that of OVA group. CD4+ percentage of IL-4 mRNA+ and IL-5 mRNA+ cells were 80.7%-82.0% and 78.0%-83.9% in post-PPD group, which were markedly lower than that of OVA group.Conclusions　Sensitization with PPD by intraperitoneal injection and then challenged by PPD inhalation markedly suppressed IL-4, IL-5 expression and eosinophil infiltration, and attenuated pulmonary Th2 reaction in ovalbumin sensitized mice. This induces Th1 type reaction and inhibits Th2 cell differentiation. It may be beneficial for glucocorticoids dependent or resistant patients.

Objective To elucidate the mechanism of anti-inflammatory effect of dexamethasone and methotrexate on pulmonary Th2 reaction and eosinophil infiltration in ovalbumin sensitized mice, and search for the possibility of aerosol administration of other anti-inflammatory drugs in the management of asthma except for glucocorticoids.Methods Sixty C57b1/6 mice were sensitized and challenged with ovalbumin, aerosol dexamethasone and methotrexate were administered after challenge. Mice lung were fixed in paraformaldehyde and IL-4, IL-5 expression was detected by immunocytochemistry-in situ hybridization. Lung slides were also stained with eosin and hematoxylin, and pathological changes were observed.Results Ovalbumin aerosol inhalation caused a mixed inflammatory infiltration dominated by CD4+ T lymphocytes and eosinophils in the lung of sensitized mice. 85.2%-88.2% and 81.4%-91.8% of the CD4+ T lymphocytes were IL-4 mRNA+ or IL-5 mRNA+ respectively, and few CD8+ T lymphocytes were IL-4 or IL-5 positive (<2%). 78.8%-80.8% of IL-4 mRNA+ cells and 78.0%-86.8%of IL-5 mRNA+ cells were CD4+ T lymphocytes. Aerosol administration of dexamethasone and methotrexate after challenge inhibited IL-4 and IL-5 expression, and lung eosinophil infiltration were attenuated. And dexamethasone was more effective. These two drugs had no effect on the ratio of IL-4 or IL-5 expression of CD4+ T lymphocytes, and the percentages of CD4+ T lymphocytes of the IL-4 mRNA+ or IL-5 mRNA+ cells were not affected. The anti-inflammatory effect was non-specific. In addition, aerosol administration of dexamethasone enhanced IL-4 expression and methotrexate promoted eosinophil infiltration 12 h after challenge.Conclusion Aerosol administration of dexamethasone and methotrexate attenuated pulmonary Th2 reaction in ovalbumin sensitized mice. Aerosol administration of drug exerts its effect at the site of inflammation, which is more effective with less side effects. But at the beginning, aerosol administration might promote inflammation. In this way, oral or intravenous injection of glucocorticoids should be given to moderate to severe asthmatic patients, and aerosol gulcocorticoids should be adminstered after the disease was under control. Methotrexate was less effective than dexamethasone but more irritative, and should not be given by inhalation, Intravenous injection of methotrexate should be administrated to asthmatic patients who respond poorly to glucocorticoids as an auxiliary therapeutic measure.