Serum PCT was a promising simple biomarker and had similar accuracy of APACHE-II scores as predicting severity of acute pancreatitis.

Aberrant expression of Notch receptors 1 and 3 play a role during cancer progression, and cytoplasmic nuclear coexistence of DLL4 expression correlates with poor survival in extrahepatic CC and gallbladder carcinoma.

Granulocyte/macrophage colony‐stimulatory factor (GM‐CSF) is an attractive adjuvant for a DNA vaccine on account of its ability to recruit antigen‐presenting cells (APCs) to the site of antigen synthesis as well as its ability to stimulate the maturation of dendritic cells (DCs). This study evaluated the utility of GM‐CSF cDNA as a DNA vaccine adjuvant for glycoprotein B (gB) of pseudorabies virus (PrV) in a murine model. The co‐injection of GM‐CSF DNA enhanced the levels of serum PrV‐specific IgG with a 1.5‐ to 2‐fold increase. Moreover, GM‐CSF co‐injection inhibited the production of IgG2a isotype. However, it enhanced production of an IgG1 isotype resulting in humoral responses biased to the Th2‐type against PrV antigen. In contrast, the co‐administration of GM‐CSF DNA enhanced the T cell‐mediated immunity biased to the Th1‐type, as judged by the significantly higher level of cytokine IL‐2 and IFN‐γ production but not IL‐4. When challenged with a lethal dose of PrV, the GM‐CSF co‐injection enhanced the resistance against a PrV infection. This suggests that co‐inoculation with a vector expressing GM‐CSF enhanced the protective immunity against a PrV infection. This immunity was caused by the induction of increased humoral and cellular immunity in response to PrV antigen.

Summary A murine model immunized with plasmid DNA vaccine expressing three glycoproteins pCIgB, pCIgC and pCIgD were used to examine the relative potency of major glycoproteins as well as the contribution of immunological parameters in providing protective immunity against the pseudorabies virus (PrV). Among the three glycoprotein-encoded plasmid DNA vaccines, pCIgB produced the strongest response of PrV-specific IgG in the sera. pCIgB and pCIgD also induced a contrast pattern of immunity that was biased to the Th1 and Th2 types, respectively. pCIgC showed the potent inducer of CD8 1 T-cell-mediated CTL activity against PrV. In addition, a cocktail vaccination of all three glycoproteinencoded plasmid DNA vaccines induced the production of both cytokine types, Th1 and Th2 with levels that were the same as that of each immunogen. With regard to protective efficacy, pCIgB induced the most effective protection against a virulent virus challenge and a cocktail vaccination appeared to offer complete protection against a 5 LD 50 challenge, but not a 10 LD 50 one. pCIgD induced protection that was same as pCIgB, but pCIgC offered no effective protection. These results show the relative potency of the three glycoprotein-encoded PrV DNA vaccines in inducing protective immunity against PrV infection. The results in this study support previous results showing the importance of Th1-type CD4 1 T cells and their antibodies in conferring protection.

SummaryChemokines play a key role in eliciting adaptive immune responses by selectively attracting the innate cellular components to the site of antigen presentation. To evaluate the effect of the genetic adjuvant of chemokines on the adaptive immune responses induced by a plasmid DNA vaccine expressing glycorotein B (gB) of the pseudorabies virus (PrV), a PrV DNA vaccine was co-inoculated with plasmid DNA expressing certain chemokines including CCL3 (MIP-1a), CCL4 (MIP-1b), CCL5 (RANTES), CXCL8 (MIP-2), and CXCL10 (IP-10). A co-injection of the CCL3 plasmid DNA induced immunity that was biased to the T helper type 2 (Th2) pattern, as judged by the ratio of immunoglobulin G isotypes and the production of interleukin-4 cytokine generated from stimulated immune T cells. However, CCL5 and CXCL10 induced immune responses of the Th1-type, which rendered the recipients more resistant to a virulent virus infection. CXCL8 also showed enhanced humoral and cell-mediated immunity (mixed-type pattern) providing effective protection against a viral challenge. However, there was no change in the immune responses induced by the PrV DNA vaccine in CCL4 recipients. These results suggest that co-injection of a chemokine, in the form of an adjuvant preparation, causes a rebalancing of the immunity, which subsequently affects the protective efficacy against a virulent virus infection.