Sensitized splenocytes result in deleterious cytokine cascade and hyperinflammatory response in rats with Pneumocystis pneumonia despite the presence of corticosteroids.
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.
Thullen
Timothy D
TD
Veterans Affairs Medical Center, Cincinnati, Ohio 45220, USA.
Ashbaugh
Alan D
AD
Daly
Kieran R
KR
Linke
Michael J
MJ
Steele
Paul E
PE
Walzer
Peter D
PD
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
D000305:Adrenal Cortex Hormones; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha