The present study shows an in vivo role for interleukin-2 in the formation of hepatic granulomatous inflammation in murine Schistosoma japonicum infection. Mice which had been administered an inhibitor to interleukin-2 function during acute infection were noted to have reduced cell-mediated immune responses to ConA and S. japonicum soluble egg antigen (SEA). Lymphoid tissue from these treated mice also have reduced numbers of cells which could be activated by ConA to produce interleukin-2 mRNA as shown by in situ hybridization studies. Mice with less activated lymphocytes had, on the average, a 70% reduction in the granulomatous inflammation surrounding eggs deposited in hepatic tissues of acutely infected mice. The data demonstrate that IL-2 is a key factor in the generation of granulomatous inflammation in S. japonicum infection and suggest that a potential anti-pathology vaccine could be generated based on limiting the presence of IL-2 generated during acute infection.

We analysed the effect of (−)-epicatechin and cocoa extract on the activation of a lymphoid cell line. Particularly the expression of IL-2 receptor α (IL-2Rα or CD25) and, the secretion of IL-2 and IL-4 were established after flavonoid treatment. Two media culture conditions (1 and 10 % of fetal calf serum supplementation) and the different moments of flavonoid addition (simultaneously or 2 h before cell-activation) were compared. IL-2Rα (CD25) expression on activated cells was significantly reduced by epicatechin and cocoa extract in a dose-dependent manner, achieving the highest inhibition of about 50 % when flavonoids were added 2 h before stimulation. IL-2 secretion was also inhibited by the presence of both epicatechin and cocoa extract, displaying 60 and 75 % of inhibition, respectively. Cocoa flavonoids were also able to enhance 3–4·5-fold IL-4 release. In summary, cocoa extract down-modulated T lymphocyte activation and therefore the acquired immune response. This fact could be important in some states of the immune system hyperactivity such as autoimmune or chronic inflammatory diseases.

Ticks are obligatory blood-feeding arthropods that secrete various immunomodulatory molecules to antagonize host inflammatory and immune responses. Cytokines play an important role in regulating these responses. We investigated the extent to which ticks interact with the sophisticated cytokine network by comparing the effect of salivary gland extracts (SGE) of 3 ixodid tick species, Dermacentor reticulatus, Amblyomma variegatum and Ixodes ricinus, all of which are important vectors of tick-borne pathogens. Using specific ELISAs, anti-cytokine activity was demonstrated with 7 cytokines: IL-8, MCP-1, MIP-1α, RANTES, eotaxin, IL-2 and IL-4. The results varied between species, and between adult males and females of the same species. Relatively high activity levels were detected in saliva of female D. reticulatus, confirming that the observed anti-cytokine activities are an integral part of tick saliva secreted into the host. Results with fractionated SGE indicated that from 2 to 6 putative cytokine binding molecules are produced, depending on species and sex. Binding ability of SGE molecules was verified by cross-linking with radio-isotope labelled MIP-1α. By targeting different cytokines, ixodid ticks can manipulate the cytokine network, which will greatly facilitate blood-feeding and provide a gateway for tick-borne pathogens that helps explain why ticks are such efficient and effective disease vectors.