Elevation of cytokines associated with the thrombocytopenia of equine infectious anaemia.
Abstract: Thrombocytopenia is a common finding in infection with equine infectious anaemia virus (EIAV), a lentivirus with some homology to human immunodeficiency virus (HIV). The thrombocytopenia of EIA, like that in some HIV patients, appears to have a multifactorial pathogenesis. To investigate the decreased platelet production seen in experimental EIA, the levels of three potential negative regulators of platelet production--tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta) and interferon-alpha (IFN-alpha)--were measured in serum and bone marrow of six severe combined immunodeficient (SCID) foals and ten immunocompetent EIAV-infected foals. Levels of cytokines in pre-infection foal sera and bone marrow were compared with levels observed during clinical EIA. Mean serum levels of TNF-alpha and IFN-alpha were significantly higher (P < 0.05) on days -4 to 0 of thrombocytopenia than before infection. Serum TGF-beta was significantly elevated on all days except day -1 of thrombocytopenia. Bone marrow TNF-alpha levels were significantly increased in infected foals just before clinical thrombocytopenia. TGF-beta activity was not different in pre-infection and pre-thrombocytopenia bone marrows, but levels of TGF-beta protein as determined by immunohistochemical staining were significantly higher in pre-thrombocytopenia bone marrow. IFN-alpha activity in bone marrow increased just before thrombocytopenia, but the difference was not significant at P < 0.05. Serum TNF-alpha levels were 2-2.5 times higher in SCID foals on three of the days prior to thrombocytopenia than in immunocompetent foals. No significant differences were found between the levels in SCID and immunocompetent foals of serum and bone marrow TGF-beta or IFN-alpha at any of the times examined.
Publication Date: 1998-02-12 PubMed ID: 9349475DOI: 10.1099/0022-1317-78-10-2541Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The research studies the role of certain cytokines in causing a reduced platelet count, or thrombocytopenia, in horses affected by equine infectious anemia virus (EIAV). The elevated levels of cytokines such as TNF-alpha, TGF-beta, and IFN-alpha were found in blood and bone marrow of horses, with TNF-alpha much higher in severely immunocompromised foals prior to thrombocytopenia.
Objective of the Study
- This study aimed to understand the multifactorial pathogenesis of thrombocytopenia, a condition characterized by a decrease in platelets in the body, associated with equine infectious anemia virus (EIAV), a lentivirus similar to the human immunodeficiency virus (HIV).
- The researchers focused on the levels of three cytokines — TNF-alpha, TGF-beta, and IFN-alpha — which are suspected to negatively regulate platelet production.
Methodology
- The study involved the analysis of serum and bone marrow samples from six severely immunodeficient (SCID) foals and ten immunocompetent EIAV-infected foals.
- The levels of cytokines in these samples, both before and during the infection, were systematically measured and compared.
Key Findings
- It was observed that the mean serum levels of TNF-alpha and IFN-alpha were significantly higher in the days leading up to the onset of thrombocytopenia.
- Similarly, bone marrow TNF-alpha levels increased significantly in infected foals just before the clinical manifestation of thrombocytopenia.
- While TGF-beta activity in bone marrow remained consistent, the protein levels of TGF-beta significantly increased before thrombocytopenia.
- IFN-alpha activity in bone marrow also showed a rise before thrombocytopenia, but it was not statistically significant.
Special Observations
- There was a marked increase of TNF-alpha levels in serum samples of SCID foals. These TNF-alpha levels were 2-2.5 times higher compared to immunocompetent foals, particularly observed just a few days prior to the onset of thrombocytopenia.
- There were no significant differences, however, within the serum and bone marrow levels of TGF-beta or IFN-alpha between SCID and immunocompetent foals.
Cite This Article
APA
Tornquist SJ, Oaks JL, Crawford TB.
(1998).
Elevation of cytokines associated with the thrombocytopenia of equine infectious anaemia.
J Gen Virol, 78 ( Pt 10), 2541-2548.
https://doi.org/10.1099/0022-1317-78-10-2541 Publication
Researcher Affiliations
- Department of Veterinary Microbiology and Pathology, Washington State University, Pullman 99164-7040, USA. tornquis@ccmail.orst.edu
MeSH Terms
- Acute Disease
- Animals
- Bone Marrow / metabolism
- Cytokines / metabolism
- Equine Infectious Anemia / complications
- Equine Infectious Anemia / metabolism
- Hematopoiesis
- Horse Diseases / immunology
- Horse Diseases / pathology
- Horses
- Infectious Anemia Virus, Equine
- Severe Combined Immunodeficiency / veterinary
- Severe Combined Immunodeficiency / virology
- Thrombocytopenia / metabolism
- Transforming Growth Factor beta / metabolism
- Tumor Necrosis Factor-alpha / metabolism
Grant Funding
- R01-HL46551 / NHLBI NIH HHS
- T3-AI07367 / NIAID NIH HHS
Citations
This article has been cited 4 times.- Detournay O, Morrison DA, Wagner B, Zarnegar B, Wattrang E. Genomic analysis and mRNA expression of equine type I interferon genes.. J Interferon Cytokine Res 2013 Dec;33(12):746-59.
- Covaleda L, Fuller FJ, Payne SL. EIAV S2 enhances pro-inflammatory cytokine and chemokine response in infected macrophages.. Virology 2010 Feb 5;397(1):217-23.
- Harrold SM, Cook SJ, Cook RF, Rushlow KE, Issel CJ, Montelaro RC. Tissue sites of persistent infection and active replication of equine infectious anemia virus during acute disease and asymptomatic infection in experimentally infected equids.. J Virol 2000 Apr;74(7):3112-21.
- Oaks JL, McGuire TC, Ulibarri C, Crawford TB. Equine infectious anemia virus is found in tissue macrophages during subclinical infection.. J Virol 1998 Sep;72(9):7263-9.
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