Endotoxins and exotoxins are among the most potent bacterial inducers of 
cytokines. During infectious processes, the production of inflammatory cytokines 
including tumor necrosis factor (TNF), interleukin-1β (IL-1β), gamma interferon 
(IFNγ) and chemokines orchestrates the anti-infectious innate immune response. 
However, an overzealous production, leading up to a cytokine storm, can be 
deleterious and contributes to mortality consecutive to sepsis or toxic shock 
syndrome. Endotoxins of Gram-negative bacteria (lipopolysaccharide, LPS) are 
particularly inflammatory because they generate auto-amplificatory loops after 
activation of monocytes/macrophages. LPS and numerous pore-forming exotoxins 
also activate the inflammasome, the molecular platform that allows the release 
of mature IL-1β and IL-18. Among exotoxins, some behave as superantigens, and as 
such activate the release of cytokines by T-lymphocytes. In most cases, 
pre-exposure to exotoxins enhances the cytokine production induced by LPS and 
its lethality, whereas pre-exposure to endotoxin usually results in tolerance. 
In this review we recall the various steps, which, from the very early discovery 
of pyrogenicity induced by bacterial products, ended to the discovery of the 
endogenous pyrogen. Furthermore, we compare the specific characteristics of 
endotoxins and exotoxins in their capacity to induce inflammatory cytokines.