The term “classical activation” of macrophages was first introduced in an infection context to describe the antigen-dependent microbicidal activity of macrophages toward bacillus Calmette-Guerin.26 M1 activation can be achieved in vitro when IFN-γ-primed cells encounter microbial products such as LPS by interacting with the extracellular receptors, resulting in a series of signaling cascade activations and the secretion of pro-inflammatory cytokines including IL-1β, IL-6, and TNF-α, and pro-inflammatory mediators such as prostaglandin E2 and NO. Here, IL1B is linked to infection.