Table 1.

Phases of the inflammatory response with characteristic features ⁽¹⁾.

Phase	Description	Characteristic Read-Outs
0 steady state	homeostatic condition	-growth, organ weight, etc. -leukocyte numbers and subset composition -steady state activities, e.g., phagocytosis
1 short-term	initiation of inflammation as response to triggering by damage- or infection-related molecules	-mast cell and basophil degranulation -neuronal activation (e.g., scratching) -reactive oxygen species (ROS) -pro-inflammatory arachidonic acid (AA) metabolites (e.g., PGE2) -phospholipase (PLA2), cyclo-oxygenase (COX-2/PTGS2) and lipoxygenase (LOX/ALOX) activity -early pro-inflammatory cytokines (IL-1, TNF, IL-6 (2))
2 short-term	amplification and regulation of inflammation; initiation of adaptive immunity	-additional pro- and anti-inflammatory cytokines (e.g., IL-12, IL-10, IL-2) -soluble forms of cellular R (e.g., sCD25, sCD163) -chemokines (e.g., CXCL8, CCL2) -induction of iNOS and nitric oxide (NO) production -anti-inflammatory AA metabolites (e.g., LXA4) -endothelial activation -edema -leukocyte mobilization and tissue infiltration -acute phase proteins (e.g., CRP) -HPA-axis activation (cortisol or corticosterone) -lymphocyte proliferation -microbial infection parameters -clearance and repair in short-term
3 short- or long-term	consequences of severe or chronic inflammation	-clearance and repair in long-term -glucose, insulin resistance, diabetes -adipokines, leptin resistance, obesity -glucocorticoid resistance, stress, hampered down-regulation of inflammation -inflammation-induced malignancy

⁽¹⁾ See Box 1 for a brief introduction on inflammation. ⁽²⁾ In the inflammatory response, IL-6 is produced in a second wave, as it has to be expressed de novo, while initial TNF and IL-1β release only requires processing (i.e., membrane cut or enzymatic cleavage and secretion, resp.). Yet, IL-6 is frequently measured together with IL-1β and TNF. Therefore, IL-6 is classified in the first phase. In itself, it is an inducer of mediators of the second phase, in particular acute phase proteins.