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

Abstract

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.

Equine PBMC Cytokines Profile after In Vitro α- and γ-EHV Infection: Efficacy of a Parapoxvirus Ovis Based-Immunomodulator Treatment

“…Our study also showed an increased IL-10 expression but no modulation of IL-1β and IL-6 mRNA. These results confirm that iPPVO stimulates the production of cytokines in equine PBMC as it was described in other species like murine, porcine, and human [ 39 , 42 , 43 ]. iPPVO was associated with stimulation of proinflammatory, Th1, and Th2 related cytokines (reviewed by [ 19 ]).…”

Orf virus: A promising new therapeutic agent

“…In terms of cellular immunity, the host antiviral defenses are activated by increasing granulocytes, accompanied by the recruitment of CD4+ T and CD8+ T cells, while the recruitment of B cells and DC need the assistance of MHC molecules . As shown in Figure , ORFV induces mainly the Th1 immune response at the early stage of infection . The peripheral immune cells secrete IFN‐γ, TNF‐α, IL‐6, IL‐8, IL‐12, and IL‐18, after which the Th2 type immune response appears, mainly inducing the secretion of IL‐4, IL‐10, and IL‐1 receptor antagonists (IL‐1RA) .…”

Effects of <i>inactive parapoxvirus ovis</i> on cytokine levels in rats

“…The amount of TNF produced is the main factor for the control of its role in the disease process [ 2 ]. IL-6 is primarily synthesized by T and B lymphocytes and by some other cells [ 1 ]. IL-6 leads to synthesis of acute phase reactants (CRP, haptoglobulin, etc.…”

“…1 ). It has been reported by Anziliero et al [ 1 ] that pro-inflammatory cytokines (TNF-α) reach to the peak level 24 hr after iPPOV inoculation in mice. Moreover, experimental models of infection (Lipopolysaccharide, LPS in rat) report that it reaches to higher concentrations in shorter times [ 26 ].…”

“…3 and 4 ). A study conducted in healthy rats has been reported 1.5 times increase in IL-10 concentration after 72 hr of iPPOV administration [ 1 ], whereas there is no study on the effect of iPPOV on IL-10 and IL-12 concentrations in viral infections. However, it is reported that IL-12 increases IFN-γ level and regulates natural killer cells in viral infection [ 14 ].…”