The attenuative effect of purified protein derivative sensitization on T helper 2 reaction and eosinophil infiltration of the lung in ovalbumin sensitized mice.
OBJECTIVE
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.
Cui
X
X
Department of Respiratory Diseases, PUMC Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Guo
Z
Z
Xu
W
W
Chen
Y
Y
Zhu
Y
Y
D000818:Animals; D004804:Eosinophils / Q000473:pathology*; D007114:Immunization; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D011897:Random Allocation; D014373:Tuberculin / Q000494:pharmacology*
D014373:Tuberculin; D010047:Ovalbumin