While the most important players of inflammation have been well described, a systematic analysis of the proteins fulfilling the effector functionalities during inflammation has not yet been undertaken. Here we present a systematic proteome study of inflammatory activated primary human endothelial cells and fibroblasts. Cells were stimulated with interleukin 1-beta and fractionated in order to obtain secreted, cytoplasmic and nuclear protein fractions. Proteins were submitted to a data-dependent bottom up analytical platform using a QExactive orbitrap and the MaxQuant software for protein identification and label-free quantification. Results were further combined with similarly generated data previously obtained from the analysis of inflammatory activated peripheral blood mononuclear cells. Applying an FDR of less than 0.01 at both peptide and protein level, a total of 8235 protein groups assembled from 163858 peptides was identified. Comparative proteome analysis allowed us to determine proteins regulated in each kind of cells during inflammation. Remarkably, cells were working on similar inflammation-related tasks, however, by regulating different proteins. Thus, we were able to determine cell type-specific inflammatory signatures, apparently resulting from cell type-specific regulatory mechanisms. Hallmarks of inflammation emerged from these findings, representing commonly and cell type-specific responsibilities of cells during inflammation.