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Clinical and vaccine immunology : CVI2011; 18(11); 1962-1968; doi: 10.1128/CVI.05034-11

Dexamethasone-induced cytokine changes associated with diminished disease severity in horses infected with Anaplasma phagocytophilum.

Abstract: Anaplasma phagocytophilum is the zoonotic cause of granulocytic anaplasmosis. We hypothesized that immune response, specifically gamma interferon (IFN-γ), plays a role in disease severity. To test this, horses were infected and IFNG expression was pharmacologically downregulated using corticosteroids. Eight horses were infected with A. phagocytophilum; 4 received dexamethasone on days 4 to 8 of infection. Clinical signs, hematologic parameters, and transcription of cytokine/chemokine genes were compared among treated and untreated horses. Infection was quantitated by msp2 real-time PCR and microscopy. As anticipated, there was significantly greater leukopenia, thrombocytopenia, and anemia in infected versus uninfected horses. The A. phagocytophilum load was higher for dexamethasone-treated horses. Dexamethasone reduced IFNG transcription by day 12 and IL-8 and IL-18 by days 7 to 9 and increased IL-4 on day 7. The ratio of IL-10 to IFNG was increased by dexamethasone on day 9. There were no hematologic differences between the infected horses. Dexamethasone suppression of proinflammatory response resulted in delayed infection-induced limb edema and decreased icterus, anorexia, and reluctance to move between days 6 and 9 and lower fever on day 7. These results underscore the utility of the equine model of granulocytic anaplasmosis and suggest that Th1 proinflammatory response plays a role in worsening disease severity and that disease severity can be decreased by modulating proinflammatory response. A role for Th1 response and macrophage activation in hematologic derangements elicited by A. phagocytophilum is not supported by these data and remains unproven.
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Publication Date: 2011-08-31 PubMed ID: 21880854PubMed Central: PMC3209032DOI: 10.1128/CVI.05034-11Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigates the impact of dexamethasone, a corticosteroid, on the immune response and disease severity in horses infected with Anaplasma phagocytophilum, a bacterium that causes granulocytic anaplasmosis. The results suggest that reducing the proinflammatory response can lessen disease severity.

Research Purpose and Hypothesis

  • The study aimed to explore the role of the immune response, specifically gamma interferon (IFN-γ), in the severity of granulocytic anaplasmosis, caused by the Anaplasma phagocytophilum bacteria.
  • The researchers hypothesized that a pharmacological downregulation of IFNG expression using corticosteroids could impact disease severity.

Methodology

  • Eight horses were infected with A. phagocytophilum, with four of them receiving dexamethasone on days 4 to 8 of infection.
  • The researchers compared clinical signs, hematologic parameters, and transcription of cytokine/chemokine genes among treated and untreated horses.
  • Infection was quantified by msp2 real-time PCR and microscopy.

Findings

  • As expected, there were more significant incidences of leukopenia, thrombocytopenia, and anemia in infected versus uninfected horses.
  • The A. phagocytophilum load was higher in dexamethasone-treated horses.
  • Dexamethasone caused a reduction in IFNG transcription by day 12, and IL-8 and IL-18 by days 7 to 9. Meanwhile, IL-4 increased on day 7.
  • Dexamethasone resulted in a delay in infection-induced limb edema and decreased icterus, anorexia, and reluctance to move between days 6 and 9 and lower fever on day 7.
  • No significant hematologic differences were found between the infected horses.

Conclusion

  • The findings demonstrate the usefulness of the equine model of granulocytic anaplasmosis and suggest that Th1 proinflammatory response plays a role in worsening disease severity.
  • The study suggests that disease severity can be decreased by modulating the proinflammatory response, but the study does not support a role for Th1 response and macrophage activation in hematologic derangements elicited by A. phagocytophilum.

Cite This Article

APA
Davies RS, Madigan JE, Hodzic E, Borjesson DL, Dumler JS. (2011). Dexamethasone-induced cytokine changes associated with diminished disease severity in horses infected with Anaplasma phagocytophilum. Clin Vaccine Immunol, 18(11), 1962-1968. https://doi.org/10.1128/CVI.05034-11

Publication

Clinical and vaccine immunology : CVI
ISSN: 1556-679X
NlmUniqueID: 101252125
Country: United States
Language: English
Volume: 18
Issue: 11
Pages: 1962-1968

Researcher Affiliations

Davies, R S
  • Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, California, USA.
Madigan, J E
    Hodzic, E
      Borjesson, D L
        Dumler, J S

          MeSH Terms

          • Anaplasma phagocytophilum / immunology
          • Anaplasma phagocytophilum / pathogenicity
          • Anemia / prevention & control
          • Animals
          • Cytokines / biosynthesis
          • Dexamethasone / administration & dosage
          • Edema / prevention & control
          • Ehrlichiosis / complications
          • Ehrlichiosis / drug therapy
          • Ehrlichiosis / pathology
          • Gene Expression Profiling
          • Horse Diseases / drug therapy
          • Horse Diseases / pathology
          • Horses
          • Immunologic Factors / administration & dosage
          • Jaundice / prevention & control
          • Real-Time Polymerase Chain Reaction
          • Severity of Illness Index

          Grant Funding

          • R01 AI041213 / NIAID NIH HHS
          • R56 AI041213 / NIAID NIH HHS
          • R01 AI41213 / NIAID NIH HHS
          • R56 AI41213 / NIAID NIH HHS

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          Citations

          This article has been cited 16 times.
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