title: Sensitized splenocytes result in deleterious cytokine cascade and hyperinflammatory response in rats with Pneumocystis pneumonia despite the presence of corticosteroids.
abstract: 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.
authors.affiliation: Veterans Affairs Medical Center, Cincinnati, Ohio 45220, USA.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Thullen
authors.forename: Alan D
authors.initials: AD
authors.lastname: Ashbaugh
authors.forename: Kieran R
authors.initials: KR
authors.lastname: Daly
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Linke
authors.forename: Paul E
authors.initials: PE
authors.lastname: Steele
authors.forename: Peter D
authors.initials: PD
authors.lastname: Walzer
mesh_terms: D019264:Adoptive Transfer; D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D007249:Inflammation / Q000209:etiology*; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008168:Lung / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D011020:Pneumonia, Pneumocystis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000305:Adrenal Cortex Hormones; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha