## 4 Discussion
### Relationship between Profile of Proinflammatory Mediators and Disease Activity
The presented moderate relationship between P-selectin and IL-1\(\alpha\) may be related to the hypothesis that the increase in IL-1\(\alpha\) emerges from the neutrophil-associated generation of free radicals, which could be mediated by the interactions of P-selectin with immune cells. The rise in oxidative stress in local inflamed tissue can stimulate the release of IL-1\(\alpha\)[21; 22]. Considering that the correlation between P-selectin and IL-1\(\alpha\) was noted only in the UC group, the P-selectin-neutrophil-IL-1\(\alpha\) axis may be involved in the development of the inflammatory state during UC, but not CD. The greater role of neutrophils in the inflammatory process during UC may be confirmed by the study conducted by [PERSON] et al. [25], in which the researchers analyzed the contribution of neutrophils to the pathogenesis of [PERSON]'s disease and ulcerative colitis. Neutrophils, upon activation, release reactive oxygen species, store enzymes in their granules, and form neutrophil extracellular traps (NETs) to neutralize potential pathogens. In [PERSON] et al. 's study, the expression of NET-associated proteins was increased in intestinal biopsies of UC patients compared to patients with CD. Additionally, upon stimulation by lipopolysaccharide and TNF-\(\alpha\), the formation of NETs by neutrophils isolated from the blood of UC patients was enhanced compared to healthy individuals, while no such correlation was noted in the CD group. The presented results indicate the primary role of neutrophils in UC compared to CD. Therefore, the observed correlation between P-selectin and IL-1\(\alpha\) may be related to the interactions of P-selectin with neutrophils and their subsequent activation inducing the local oxidative stress, leading to the release of IL-1\(\alpha\). The observed moderate correlation between E-selectin and IL-12p70 serum levels may also be explained by the interaction of adhesive molecules with immune cells. E-selectin binds to ligands located on the surface of neutrophils, monocytes, and T cells [10]. The binding of monocytes to E-selectin was related in the study by [PERSON] et al. [26] with the phosphorylation of protein kinase B (also known as AKT) in human monocytes. The activation of AKT is suggested to fulfill an antiapoptotic role; therefore, the observed upregulation of AKT upon binding to E-selectin may prolong the survival of monocytes after migration to inflamed tissue. However, these results were not observed in the case of P-selectin, indicating that AKT activation in monocytes is limited to the binding of these immune cells to E-selectin. Regarding the fact that IL-12p70 is released from, among others, macrophages, the observed relationship may be related to the prolonged survival of macrophages releasing IL-12p70 upon ligation with E-selectin. The inflammatory mediator that correlated most often with other analyzed biomarkers in this study was TNF-\(\alpha\), which is a pleiotropic cytokine with a well-established role in the development of ulcerative colitis. TNF-\(\alpha\) is engaged in the activation of macrophages, the amplification of the T cell response, and the increase in the expression of adhesive molecules. In this research, we noted a significant moderate correlation between the level of TNF-\(\alpha\) and E-selectin in the serum of patients with UC. The influence of TNF-\(\alpha\) on the expression of adhesive molecules can be confirmed by [PERSON] et al. 's [27] study, in which TNF-\(\alpha\) increased the expression of E-selectin in human umbilical vein endothelial cells (HUVECs). This effect of TNF-\(\alpha\) on E-selectin expression was not only intermittent, but also reversed by the exposition of the HUVEC cell culture to anti-TNF-\(\alpha\) antibodies. These findings confirm the relationship between TNF-\(\alpha\) and E-selectin observed in our study. Another significant and moderate relationship was noted in the case of the TNF-\(\alpha\) and CCL-2 serum profile in the UC group.