Resolution of Pneumocystis murina infection following withdrawal of corticosteroid induced immunosuppression.
The host response during resolution of Pneumocystis murina infection following withdrawal of Dexamethasone (Dex) induced immunosuppression was analyzed. Mice were inoculated with P. murina and treated with Dex for 4 weeks. Treatment was stopped and mice were sacrificed at d1, d7, and d14. Control mice were treated in the same manner, but were inoculated with nonviable P. murina. P. murina was actively cleared from the lungs following withdrawal of Dex treatment. No P. murina was detected in control mice. Significantly more neutrophils, lymphocytes, macrophages, and eosinophils were recovered from the lungs of mice that had been infected with P. murina than from control mice at d7, but only neutrophils remained significantly elevated at d14. Significantly more CD4+ and CD8+ T cells were purified from the lungs of mice that had been infected with P. murina mice at d7 and d14. Cytokine levels were measured in lung lavage fluid by ELISA. TNF-alpha, IFN-gamma, IL-1, and IL-6 levels were higher in mice that had been inoculated with P. murina at all three time points. TNF-alpha and IL-1 levels did not change significantly following withdrawal of Dex treatment. Low levels of IL 6 were detected at d1, but increased significantly by d7 and d14. IFN-gamma levels peaked at d14. Chemokine message levels were measured in lung tissue by ribonuclease protection assay. MIP-1beta and IP-10 message increased between d1 and d7 and then decreased by d14. RANTES message levels increased from d1 to d7 and remained elevated at d14. Withdrawal of Dex induced immunosuppression from P. murina infected mice resulted in activation of many arms of the host response that lead to resolution of the infection.
Linke
Michael
M
Department of Veterans Affairs Medical Center, Research Service, Cincinnati, OH 45220, USA. michael.linke@med.va.gov
Ashbaugh
Alan
A
Demland
Jeffery
J
Koch
Judith
J
Tanaka
Reiko
R
Walzer
Peter
P
D000818:Animals; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D003907:Dexamethasone / Q000008:administration & dosage; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007111:Immunity, Cellular; D007165:Immunosuppression Therapy; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D051379:Mice; D023421:Models, Animal; D011020:Pneumonia, Pneumocystis / Q000276:immunology* / Q000628:therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology; D016896:Treatment Outcome
D016207:Cytokines; D003907:Dexamethasone