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Infection and Immunity, February 2004, p. 757-765, Vol. 72, No. 2
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.2.757-765.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Sensitized Splenocytes Result in Deleterious Cytokine Cascade and Hyperinflammatory Response in Rats with Pneumocystis Pneumonia despite the Presence of Corticosteroids

Timothy D. Thullen,1,2,3 Alan D. Ashbaugh,2 Kieran R. Daly,2 Michael J. Linke,1,2 Paul E. Steele,3,4 and Peter D. Walzer1,2,3*

Veterans Affairs Medical Center,1 Division of Infectious Disease, Department of Internal Medicine,2 Department of Pathology, University of Cincinnati College of Medicine,3 Department of Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio4

Received 25 August 2003/ Returned for modification 24 September 2003/ Accepted 10 November 2003

The immune response to the opportunistic pulmonary pathogen Pneumocystis can have beneficial and harmful effects on the host despite the presence of corticosteroids. We hypothesized that this deleterious hyperinflammatory response is associated with exaggerated cytokine production. The adoptive transfer of at least 107 immune splenocytes reduced the cyst count in rats with corticosteroid-induced pneumocystosis. About 18% of these rats developed clinical illness, an increased lung weight/body weight (LW/BW) ratio, and elevated levels of interleukin 1{alpha} (IL-1{alpha}), IL-1ß, IL-6, tumor necrosis factor alpha, IL-5, IL-10, and gamma interferon in the lungs. This hyperinflammatory reaction was not observed in rats that remained clinically well or in control rats. Thus, in this model, corticosteroids have little effect on the cytokine cascade or other adverse effects of the host immune response to Pneumocystis.

* Corresponding author. Mailing address: Research Service (151), VA Medical Center, 3200 Vine St., Cincinnati, OH 45220. Phone: (513) 475-6338. Fax: (513) 475-6415. E-mail: peter.walzer{at}med.va.gov.

Editor: T. R. Kozel

Infection and Immunity, February 2004, p. 757-765, Vol. 72, No. 2
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.2.757-765.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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