Systems biology description of inflammation in human skin.

(A) Under normal conditions the homeostasis (defined by the dose-dependent cytokine production curve intersection) is reached at one steady-state point at low cytokine concentration levels. Combinations of SNPs and modified cytokine expression levels observed in disease can cause more than one stable (B) or unstable (C) homeostasis. In case of additional stable cytokine level (B), the interacting immune cell populations represent a trigger that can switch and remain in the state of either low or high cytokine concentration levels. When the combination of genetic alterations causes an additional homeostasis point which is unstable with a limit cycle, the cytokine levels can oscillate both locally and spatiotemporally. In such case, the inflammatory cytokines are more likely to be distributed more unevenly across the site of inflammation causing a skin inflammation phenotype of heterogeneous nature (C).