Open AccessSensitized Splenocytes Result in Deleterious Cytokine Cascade and Hyperinflammatory Response in Rats withPneumocystisPneumonia despite the Presence of Corticosteroids
Author(s) -
Timothy D. Thullen,
Alan Ashbaugh,
Kieran R. Daly,
Michael J. Linke,
Paul E. Steele,
Peter D. Walzer
Publication year - 2004
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.72.2.757-765.2004
Subject(s) - immunology , immune system , cytokine , tumor necrosis factor alpha , interferon gamma , splenocyte , adoptive cell transfer , biology , interleukin , pneumocystis pneumonia , corticosteroid , medicine , t cell , pneumocystis jirovecii , human immunodeficiency virus (hiv)
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 10(7) 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 1alpha (IL-1alpha), IL-1beta, 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.