Monocyte-based models for describing the human inflammatory response in physiological and pathological conditions.

The human inflammatory response in a tissue has been modelled in vitro by culturing human normal monocytes isolated from blood in conditions that sequentially reproduce the recruitment from blood into the inflamed site, the encounter with the infectious agents, the subsequent development of an inflammatory reaction ending up with the destruction of the triggering agent, and the eventual resolution with tissue repair and re-establishment of homeostasis. By changing the culture conditions, we could also reproduced the conditions of persistent/chronic inflammation typical of a non-resolving disease. The course of inflammation in the two models was profiled by transcriptome analysis using RNA-Seq, taking the IL-1 family genes as reference. Gene expression of six cytokines (IL1B, IL1A, IL1RN, IL18, IL18BP, IL36G) and four receptors (IL1R1, IL1R2, IL1RAP, SIGIRR) is similarly regulated during the early phase of the acute and chronic inflammatory responses. Expression of most of these genes returned to the low basal level during the resolution phase in the acute model, while it was higher than in fresh monocytes in the late phases of the chronic model. Exceptions are the two inhibitor genes IL18BP and SIGIRR. The GSEA analysis revealed that in both acute and chronic inflammation the expression of all the IL-1 family genes is mainly modulated during the first 14 h, whereas they remain practically unchanged between 72 and 96 h in the chronic model. These data suggest that the IL-1 related cytokines and receptors can be useful biomarkers to discriminating between physiological and pre-pathological inflammatory reactions.