Summary Introduction. Cervical cancer is the fourth most common form of cancer in women [19]. The precancerous stages are divided into three distinctive stages, labelled cervical intraepithelial neoplasia (CIN) I, II and III. One of the aetiological factors is chronic inflammation in cervical tissue, most often induced by Human papilloma virus (HPV). 88,5% of the patients regress from low grade intraepithelial changes to unchanged epithelium [14]. It has been proposed that cytokine balance plays a key role in the development of high grade epithelial changes (CIN I – CIN III) in the remaining 11.5% of patients, however, the exact trigger of this event remains to be found. Aim of the Study. The aim of the study was to determine three pro-inflammatory (IL-1α, IL-6, IL-8) and one anti-inflammatory (IL-10) interleukin expression in different CIN cervix uteri biopsies. Material and methods. 16 biopsies were obtained with different CIN staging: one with CIN I stage, five with CIN II stage and 10 with CIN III stage. The samples were stained with haematoxylin and eosin and immunohistochemistry for IL-1α, IL-6, IL-8 and IL-10. Slides were evaluated semi-quantitatively grading the intensity of positively stained structures in the visual field. Results. Examination of the samples yielded the following: IL-1α expression increased from CIN II to CIN III in squamous epithelium, while IL-8 expression decreased. A few IL-1α containing inflammatory cells were found in all CIN stages. IL-8 expression in subepithelium and the number of inflammatory cells decreased from CIN II stage to CIN III, although, it increased in the blood vessel endothelium. Conclusions. There was constant moderate expression of both IL-6 and IL-10 during all CIN stages, except for inflammatory cells, where IL-6 expression was high during all stages, yet there were few IL-10 containing cells during CIN. The balanced expression of both cytokines suggests that pro- and anti-inflammatory cytokine balance has an important role in CIN morfopathogenesis. The high expression of IL-6 in inflammatory cells and constant expression trough CIN staging indicates sustentation of chronic inflammation and production of other cytokines, such as IL-8, IL-1α. The variable IL-8 expression and its decrease in CIN III stage suggests the depletion of IL-8 production. The high expression of cytokines in blood vessel endothelium indicates their important role in CIN morfopathogenesis.

Objective: To detect the appearance and distribution of factors regulating remodeling, innervation, growth, and vascularity of the nasal tissue affected by cleft lip and palate (CLP). Design: Morphological analysis of human tissue. Setting: Cleft and craniofacial center. Participants: Fifteen patients who underwent CLP rhinoplasty, 7 control patients. Interventions: Rhinoplasty. Main Outcome Measures: Immunohistochemistry was performed with protein gene product (PGP) 9.5, transforming growth factor β1 (TGFβ1), vascular endothelial growth factor (VEGF), cluster of differentiation 34 (CD34), matrix metalloproteinase 2 (MMP2), MMP9, and tissue inhibitor of metalloproteinase 2 (TIMP2). The results were evaluated semiquantitatively. Spearman rank order correlation coefficient and Mann-Whitney U test were used for statistical analysis. Results: Cleft lip and palate–affected tissue revealed dense and loose connective tissue, adipose cells, and hyaline cartilage, along with numerous CD34-positive endotheliocytes and regions of VEGF-positive neoangiogenesis. We observed moderate to numerous PGP 9.5-positive nerve fibers. Transforming growth factor β1, MMP2, MMP9, and TIMP2 were found in cartilage and connective tissue. Cleft lip and palate–affected tissue compared to control samples showed a statistically significant difference in PGP 9.5 ( P = .006), VEGF ( P = .001), MMP2 ( P = .002), MMP9 ( P = .013), and TIMP2 ( P < .001) expression. We observed a strong, positive correlation between VEGF and MMP9 ( P = .027; r S = 0.705). Conclusions: The moderate expression of TGFβ1 and increased distribution of VEGF, MMP2, MMP9, and TIMP2 demonstrate an active extracellular matrix remodeling and angiogenesis, performed by proteases. The cartilaginous septum of the nose is an example of balance between tissue degradation and its suppression, demonstrated by the relationship between MMPs and TIMPs and the presence of VEGF.

The craniofacial region forms in a complicated developmental process regulated by multiple genes and growth factors. Disruption and dysregulation during facial development can lead to multiple congenital facial anomalies including cleft lip and palate. This literature review collects and analyses the existing information about the interaction of multiple growth factors and genes within the developing facial region and their association with facial pathology. The factors analysed in this review are DLX4, FOXE1, HOXB3, MSX2, PAX7, PAX9, RYK, SHH, SOX3, WNT3A, WNT9B and BARX1.