Gender-Specific Cytokine Pathways, Targets, and Biomarkers for the Switch from Health to Adenoma and Colorectal Cancer
Figure 1
Relationships using the whole blood assay method (72h assay, black): (black triangle) Positive relationships. Relationships using PBMC cells separated by Ficoll/Hypaque gradient procedures (24 h assay, white): (white triangle) positive and (crescent shape) negative relationships. Basic Condition: resting state; +LPS: APC activated condition; +PHA: T cell activated condition. Basic condition (b), LPS (L), PHA (p). In healthy subjects, differences in the relationships in the “level network profiles” could be responsible for the sexual dimorphism of the immune response in health. Gender-specific relationships in “level network profiles” affect the direction (Th1 or Th2) of the immune response under resting (Basic) and activated (+PHA) conditions. APCs (+LPS) regulate the starting type and evolution of immunological responses in both men and women: the starting type (+LPS → Basic,) appears to be regulated by IFNγ production in men, and by IL6 in women; the evolution (+LPS → +PHA) by continuing IL6 production in women and by IFNγ in men. No significant relationships were found in whole blood culture supernatants without stimulus (basic conditions) in men. In women, this regulation would appear to be exerted by the linked production of IL2, IL4 and IFNγ, IL6 cytokines (relationships in basic conditions). The IL2 and IL4 interregulation in women seems to have both an early and late role since the correlation between their levels are significant in both the 24h and 72h culture supernatant cytokine assays; the interregulation between IL6 and IFNγ levels only has a late function because it is only significant in the 72h assay. The earlier evolution of activated T cells (+PHA 24h culture) seems to be influenced by the linked production of IL6 and IL4, IFNγ and IL10 cytokines in men; while by IL6 and IL10 cytokines in women. The late evolution of activated T cells (+PHA 72h whole blood of culture) on the other hand seems to be influenced by the linked production of IFNγ and IL4 in men, while by IFNγ and IL6 in women.
