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An eco-epidemiological system incorporating a vertically transmitted infectious disease is proposed and investigated. Micheal-Mentence type of harvesting is utilized to study the harvesting effort imposed on the predator. All the properties of the solution of the system are discussed. The dynamical behaviour of the system, involving local stability, global stability, and local bifurcation, is investigated. The work is finalized with the numerical simulation to observe the global behaviour of the solution.

A prey-predator model with Michael Mentence type of predator harvesting and infectious disease in prey is studied. The existence, uniqueness and boundedness of the solution of the model are investigated. The dynamical behavior of the system is studied locally as well as globally. The persistence conditions of the system are established. Local bifurcation near each of the equilibrium points is investigated. Finally, numerical simulations are given to show our obtained analytical results.

In the current paper, the effect of fear in three species Beddington–DeAngelis food chain model is investigated. A three species food chain model incorporating Beddington-DeAngelis functional response is proposed, where the growth rate in the first and second level decreases due to existence of predator in the upper level. The existence, uniqueness and boundedness of the solution of the model are studied. All the possible equilibrium points are determined. The local as well as global stability of the system are investigated. The persistence conditions of the system are established. The local bifurcation analysis of the system is carried out. Finally, numerical simulations are used to investigate the existence of chaos and understand the effect of varying the system parameters. It is observed that the existence of fear up to a critical value has a stabilizing effect on the system; otherwise it works as an extinction factor in the system.

We studied the effects of two Salmonella enterica serovar Typhimurium (host-adapted) strains (14028 and 4/74) and three S. Choleraesuis (non-host-adapted) strains (A50, A45, and B195) in human monocytes between 2 and 24 h postinfection (p.i.) to investigate whether differences in immune response may explain the much higher prevalence of sepsis in individuals infected with S. Choleraesuis. Both serovars significantly increased the production of cytokines associated with acute sepsis (tumor necrosis factor alpha [TNF-α], interleukin β [IL-β], and IL-6), but temporal differences occurred between these serovars and between different S. Choleraesuis strains. Generally, all S. Choleraesuis strains induced significantly higher production of inflammatory cytokines than S. Typhimurium strains (P < 0.01 to 0.05). All S. Choleraesuis strains very significantly increased IL-10 production by monocytes at 6 and 24 h p.i. in comparison to S. Typhimurium strains (P < 0.01). In addition, ∼80% of monocytes were viable at 24 h p.i. with S. Choleraesuis A50, compared to only ∼40% following S. Typhimurium infection. Using S. Typhimurium 14028 and S. Choleraesuis A50 as examples of these two serovars, we also showed differential expression of genes within the Janus tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT) (JAK/STAT) pathway via quantitative PCR (qPCR) microarray analysis. High serum IL-10 concentration and monocyte survival have been reported as markers of the development of human sepsis. We therefore conclude that high production of IL-10 by monocytes may, in part, explain the greater propensity for S. Choleraesuis to induce human sepsis and that this may be greater in strains such as A50, which induces both high IL-10 production and monocyte survival.

We compared the effect of VIP on human blood monocytes infected with Salmonella typhimurium 4/74 or stimulated with LPS. VIP (10−7 M) increased monocyte viability by 24% and 9% when cultured for 24 h with 4/74 or Salmonella LPS (100 ng/ml), respectively. Significantly increased (P < 0.05) numbers of 4/74 were also recovered from monocytes co-cultured with VIP after 6 h post-infection (pi) and this remained high after 24 h pi. Both 4/74 and LPS increased (P < 0.05) the concentration of TNF-α, IL-1β and IL-6 measured in monocyte supernatants. However, LPS induced this effect more rapidly while, with the exception of IL-6, 4/74 induced higher concentrations (P < 0.05). VIP significantly decreased (P < 0.05) TNF-α and IL-1β production by 4/74-infected monocytes after 6 pi, but only after 24 h in LPS-cultured monocytes. This trend was reversed for IL-6 production. However, TNF-α and IL-1β production by 4/74-infected monocytes, cultured with VIP, still remained higher (P < 0.05) than concentrations measured in supernatants cultured only with LPS. VIP also increased (P < 0.05) production of anti-inflammatory IL-10 in both 4/74 and LPS cultures after 24 h. We also show a differential effect of VIP on the expression of TNFα and IL-6 receptors, since VIP was only able to decreased expression in LPS-stimulated monocytes but not in 4/74-infected monocytes. In conclusion, we show a differential effect of VIP on human monocytes infected with virulent Salmonella or stimulated with LPS. Our study suggests that the use of VIP in bacteraemia and/or sepsis may be limited to an adjunctive therapy to antibiotic treatment.

Murine/LPS models of Gram negative sepsis indicate that vasoactive intestinal peptide (VIP) has therapeutic potential. We investigated the unknown effect of VIP on JAK/STAT proteins and genes in human monocytes infected with Salmonella Typhimurium 14028. S. Typhimurium 14028 increased expression of both IL-6 receptor (IL-6R) and interferon gamma receptor 1 (IFNγR1) on monocytes but co-culture of infected monocytes with VIP (10-7 M) only decreased expression of IFNγR1 (P < 0.05). In contrast, S. Typhimurium 14028 infection or co-culture with VIP had no effect on IL-10 receptor expression on the monocyte surface. However, S. Typhimurium 14028 down regulated IFNGR1 gene expression and this was not altered by co-culture with VIP, suggesting that changes in IFNγR1 protein may be due to an effect on cytoplasmic transport. 15 JAK/STAT genes, out of 84 studied, were up-regulated by S. Typhimurium 14028 infection and five were down-regulated. Co-culture with VIP significantly decreased expression of two genes (IFNG and IL-20) and increased expression of three genes (SOCS1, SOCS3 and STAT4) (P < 0.05). S. Typhimurium 14028 also increased expression of PTPN1, which dephosphorylates JAK2 and TYK2. This was unaltered by co-culture with VIP but S. Typhimurium 14028-induced expression of ISG15, associated with susceptibility to Gram negative infection, was further increased by VIP. We conclude that the effect of VIP on JAK/STAT genes may preclude its therapeutic use in human Gram negative sepsis.

Despite great medical advancement in the treatment of cancer, cancer remains a disease of global significance. Chemotherapeutics can be very expensive and drain medical resources at a national level and in some cases the cost of treatment is so great that it prohibits their use by local health authorities. Drug resistance is also a major limiting factor to the successful treatment of cancer with many patients initially responding well but then becoming refractory to treatment with the same drug and in some case may become multi-drug resistant. The immune system is known to be important in the prevention of tumors by eliminating pre-cancerous or cancerous cells. This concept of immune surveillance has largely been super-ceded by the concept of immunoediting whereby the immune system imposes a selective pressure on tumor cells which may either control tumor growth or inadvertently select for tumor cells which have evolved to escape the immune response and which may induce tumor development. Stimulation of the immune system by vaccination offers many benefits in the treatment of cancer. It is highly cost effective and vaccines can be manipulated to include multi-antigens which in some cases may overcome equilibrium (and selective pressure) while also preventing the establishment of reactivated cancer cells, since cancer antigen-specific memory would be induced following the initial vaccination/booster phase. To date studies using vaccination as a treatment for cancer have been a little disappointing, probably due to insufficient level of immunogenicity. In this review we will discuss methods of manipulation of the immune system to increase the anti-cancer activity of dendritic cells in vivo and how monocyte derived dendritic cells may be manipulated ex vivo to provide more robust, patient-specific treatments.

Gram negative sepsis remains a high cause of mortality and places a great burden on public health finance in both the developed and developing world. Treatment of sepsis, using antibiotics, is often ineffective since pathology associated with the disease occurs due to dysregulation of the immune system (failure to return to steady state conditions) which continues after the bacteria, which induced the immune response, have been cleared. Immune modulation is therefore a rational approach to the treatment of sepsis but to date no drug has been developed which is highly effective, cheap and completely safe to use. One potential therapeutic agent is VIP, which is a natural peptide and is highly homologous in all vertebrates. In this review we will discuss the effect of VIP on components of the immune system, relevant to gram negative sepsis, and present data from animal models. Furthermore we will hypothesise on how these studies could be improved in future and speculate on the possible different ways in which VIP could be used in clinical medicine.

Vasoactive intestinal peptide (VIP) is a pleiotropic, highly conserved, peptide found in many different biological systems throughout invertebrate phyla. VIP is produced by cells of the immune system but also inhibits many different inflammatory products produced by these immune cells, including cytokines and chemokines. VIP inhibits these immune mediators by affecting transcriptional regulators such as NFκB and activator protein 1 which transcribes genes responsible for the production of inflammatory mediators in response to pathogens or cytokines. In this review, the therapeutic potential of VIP will be discussed in the context of transcriptional regulation of immune cells in in vitro and in vivo animal models.