title: 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.
authors: Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, California, USA.
authors: R S
authors: RS
authors: Davies
authors: J E
authors: JE
authors: Madigan
authors: E
authors: E
authors: Hodzic
authors: D L
authors: DL
authors: Borjesson
authors: J S
authors: JS
authors: Dumler
mesh_terms: D041081:Anaplasma phagocytophilum / Q000276:immunology / Q000472:pathogenicity*; D000740:Anemia / Q000517:prevention & control; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D003907:Dexamethasone / Q000008:administration & dosage*; D004487:Edema / Q000517:prevention & control; D016873:Ehrlichiosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D020869:Gene Expression Profiling; D006734:Horse Diseases / Q000188:drug therapy* / Q000473:pathology; D006736:Horses; D007155:Immunologic Factors / Q000008:administration & dosage*; D007565:Jaundice / Q000517:prevention & control; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D003907:Dexamethasone