Activity of the Toll-like receptor ligands in children with high and low socioeconomic backgrounds

Background: Adjuvants are essential in the induction of immunity by vaccines and interact with receptors, including the Toll-like receptors (TLRs). Responsiveness of these receptors differs between and within populations, which impacts vaccine effectiveness. Objective: Here we examine how the innate cytokine response towards TLR ligands differs between high and low socioeconomic status (SES) school-aged children from Makassar, Indonesia. Methods: We stimulated whole blood from children, of which 27 attended a high SES school and 27 children a low SES school, with ligands for TLR-2/1, -2/6, -3, -4, -5, -7, -9 and measured pro- (TNF) and anti-inflammatory (IL-10) cytokines released. Results: In the low SES there is an increased pro-inflammatory response after 24 h stimulation with TLR-2/1 ligand Pam3 and TLR-4 ligand LPS compared to the high SES. Comparison of the response to LPS after 24 h versus 72 h stimulation revealed that the pro-inflammatory response in the low SES after 24 h shifts to an antiinflammatory response, whereas in the high SES the initial anti-inflammatory response shifts to a strong proinflammatory response after 72 h stimulation. Conclusion: We observed differences in the TLR-mediated innate immune response between children attending low and high SES schools, which can have important implications for vaccine developmentHost-parasite interactio

Erythrodermic psoriasis: Current and future role of biologicals

Erythrodermic psoriasis (EP) is a severe form of psoriasis that may be associated with serious and sometimes fatal complications. The treatment of EP is often a challenge, since several factors, including treatment failure or possible complications, may limit favorable outcomes with traditional drugs. Recent evidence suggests that biological drugs, including both anti-tumor necrosis factor alpha agents and ustekinumab, may be useful in improving the management of EP. Unfortunately, since subjects with EP are usually excluded from pivotal trials involving biological agents, this evidence is currently dispersed in small case series and single case reports. In this paper, we briefly analyze conventional therapies for EP, before going on to critically evaluate the existing clinical evidence for the role of current biological drugs, namely infliximab, etanercept, adalimumab, and ustekinumab. Finally, we discuss the potential benefits that newer/developmental biological agents could bring to the management of EP