Captive cheetah (Acinonyx jubatus) populations worldwide are plagued by debilitating diseases that are rare in free-ranging cheetahs exposed to the same infectious agents.3 The prototype disease is Helicobacter gastritis because of striking differences in prevalence of moderate to severe disease between captive (64%) and free-ranging (3%) cheetah populations infected with the same Helicobacter types.6 Captive cheetahs also have adrenal cortical hyperplasia and higher corticoids than free-ranging cheetahs, suggesting chronic stress.7 Corticoids have many complex effects on the immune system including altering gene expression of some cytokines, inflammatory mediators, and cell receptors that determine the host's response to infectious agents.1 Specifically, corticoids are known to decrease expression of interleukin (IL)-1, -2 and interferon (IFN)γ genes, thereby suppressing cell-mediated immunity and shifting the immune system toward antibody-dominant responses.5 The lesions that captive cheetahs develop to many infectious agents are largely plasmacytic, typical of antibody-dominant responses, suggesting modulation by elevated corticoids.2,4
To determine if elevated corticoids in captive cheetahs have altered the local gastric immune response, concentrations of IL-1, IL-2, and IFNγ mRNA were measured in the gastric mucosa of 30 cheetahs infected with Helicobacter, 15 captive cheetahs with moderate to severe gastritis, and 15 free-ranging cheetahs without gastritis. RNA for tumor necrosis factor (TNF)α and MHC II, which are generally expressed in inflammation, were also quantified in the same samples in order to further characterize the inflammatory response. RNA was measured by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) using cheetah specific primers. Concentrations of MHC II and TNFα, general inflammatory mediators that are not known to be affected by corticoids, were appropriately higher in cheetahs with gastritis. In contrast, concentrations of IFNγ and IL-1, general inflammatory cytokines whose expression can be suppressed by corticoids, were not elevated in cheetahs with gastritis suggesting an inappropriately suppressed expression in these cheetahs. Additionally, IL-2, an inflammatory cytokine normally present at low levels but known to be suppressed by corticoids, could not be detected in captive cheetahs with gastritis. These results suggest that higher levels of corticoids in captive cheetahs have inappropriately altered local gastric cytokine expression. Because relative levels of these cytokines determine the character of and drive the immune response, this altered cytokine expression in captive cheetahs has likely modulated the normal immune response towards an intense plasmacytic inflammatory reaction and immune-mediated damage to the gastric mucosa. Further research should evaluate whether immune responses in captive cheetahs are similarly modulated in response to other infectious agents.
The authors wish to thank the Cheetah Conservation Fund, The Living Desert, Sacramento Zoo, White Oak Conservation Center and Wildlife Safari for contributing samples for this research. The authors also wish to thank Ms. Stacy Schultz and Dr. Brian Aldridge for technical assistance, the Brookfield Zoo and the Loyola University Molecular Core Facility. This study was generously funded by the Morris Animal Foundation.
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