Abstract
Feline immunodeficiency virus (FIV) induces opportunistic disease in chronically infected cats, and both prednisolone and cyclosporine A (CsA) are clinically used to treat complications such as lymphoma and stomatitis. However, the impact of these compounds on FIV infection are still unknown and understanding immunomodulatory effects on FIV replication and persistence is critical to guide safe and effective therapies. To determine the immunologic and virologic effects of prednisolone and CsA during FIV infection, FIV-positive cats were administered immunosuppressive doses of prednisolone (2 mg/kg) or CsA (5 mg/kg). Both prednisolone and CsA induced acute and transient increases in FIV DNA and RNA loads as detected by quantitative PCR. Changes in the proportion of lymphocyte immunophenotypes were also observed between FIV-infected and naïve cats treated with CsA and prednisolone, and both treatments caused acute increases in CD4+ lymphocytes that correlated with increased FIV RNA. CsA and prednisolone also produced alterations in cytokine expression that favored a shift toward a Th2 response. Pre-treatment with CsA slightly enhanced the efficacy of antiretroviral therapy but did not enhance clearance of FIV. Results highlight the potential for drug-induced perturbation of FIV infection and underscore the need for more information regarding immunopathologic consequences of therapeutic agents on concurrent viral infections.
Highlights
Feline immunodeficiency virus (FIV) is a naturally occurring lentivirus of domestic cats that produces progressive immune depletion resulting in an AIDS-like syndrome [1,2,3,4,5,6,7,8,9,10]
interleukin 2 (IL-2) expression plays a central role in the proliferation and activation of effector and memory T-lymphocytes, and both prednisolone and cyclosporine A (CsA) exhibit a similar impact on this important regulatory pathway [39,40]
Immunosuppressive doses of CsA and prednisolone in FIV-infected cats transiently exacerbated FIV replication rates in conjunction with acute increases in the proportion of CD4+ lymphocytes and increased proviral loads. The mechanisms driving these changes are not yet apparent, this evidence suggests that direct interplay between drug-induced immunosuppression and shifts in circulating lymphocyte populations may result in transient increases in FIV replication, which may result in higher levels of proviral
Summary
Feline immunodeficiency virus (FIV) is a naturally occurring lentivirus of domestic cats that produces progressive immune depletion resulting in an AIDS-like syndrome [1,2,3,4,5,6,7,8,9,10]. Similar to human immunodeficiency virus (HIV), FIV-infected cats may develop secondary or opportunistic infections as a consequence of viral-induced immune dysfunction, including anterior uveitis, chronic rhinitis, gingivostomatitis and periodontitis, encephalitis and neurologic dysfunction, and lymphoma [10,11,12,13,14,15,16,17,18,19]. Adjunct therapies are frequently used in the clinical environment to ameliorate symptoms of secondary diseases associated with FIV infection, including prednisolone and cyclosporine A (CsA), but the effects of these compounds on FIV infection kinetics are unknown [23,24,25,26,27,28,29,30,31,32]. IL-2 expression plays a central role in the proliferation and activation of effector and memory T-lymphocytes, and both prednisolone and CsA exhibit a similar impact on this important regulatory pathway [39,40]
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