Inactivated Parapoxvirus ovis induces a transient increase in the expression of proinflammatory, Th1-related, and autoregulatory cytokines in mice

• Published in: Brazilian journal of medical and biological research 2014-02, Vol.47 (2), p.110-118
• Main Authors: Anziliero, D, Weiblen, R, Kreutz, L C, Spilki, F, Flores, E F
• Format: Article
• Language: English
• Subjects: Analysis; Animals; BIOLOGY; Biomedical Sciences; Cytokine; Cytokines; Cytokines - blood; Cytokines - immunology; Cytokines - metabolism; DNA, Complementary - biosynthesis; Encephalomyocarditis virus; Enzyme-Linked Immunosorbent Assay; Female; Immune response; Immunostimulant; Innate immune response; MEDICINE, RESEARCH & EXPERIMENTAL; Messenger RNA; Mice; mRNA; ORF virus; Orf virus - immunology; Ovis; Parapoxvirus; Parapoxvirus - immunology; Real-Time Polymerase Chain Reaction; RNA, Messenger - metabolism; Th1 Cells - metabolism; Th1 Cells - virology; Time Factors; Tumor necrosis factor
• ISSN: 0100-879X; 1414-431X; 1414-431X; 0100-879X
• DOI: 10.1590/1414-431x20133358

The immunostimulatory properties of inactivated Parapoxvirus ovis (iPPVO) have long been investigated in different animal species and experimental settings. In this study, we investigated the effects of iPPVO on cytokine expression in mice after intraperitoneal inoculation. Spleen and sera collected from iPPVO-treated mice at intervals after inoculation were submitted to cytokine mRNA determination by real-time PCR (qPCR), serum protein concentration by ELISA, and interferon (IFN)-α/β activity by bioassay. The spleen of iPPVO-treated animals showed a significant increase in mRNA expression of all cytokines assayed, with different kinetics and magnitude. Proinflammatory cytokines interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α), and IL-8 mRNA peaked at 24 hours postinoculation (hpi; 5.4-fold increase) and 48 hpi (3- and 10-fold increases), respectively. A 15-fold increase in IFN-γ and 6-fold IL-12 mRNA increase were detected at 48 and 24 hpi, respectively. Increased expression of autoregulatory cytokines (Th2), mainly IL-10 and IL-4, could be detected at later times (72 and 96 hpi) with peaks of 4.7- and 4.9-fold increases, respectively. IFN-I antiviral activity against encephalomyocarditis virus was demonstrated in sera of treated animals between 6 and 12 hpi, with a >90% reduction in the number of plaques. Measurement of serum proteins by ELISA revealed increased levels of IL-1, TNF-α, IL-12, IFN-γ, and IL-10, with kinetics similar to those observed by qPCR, especially for IL-12 and IFN-γ. These data demonstrate that iPPVO induced a transient and complex cytokine response, initially represented by Th1-related cytokines followed by autoregulatory and Th2 cytokines.