## 3 Results and Discussion
### Carboxymethylcellulose Characterization
#### 3.1.5 Interleukins Production  
While inflammatory processes in the skin are widely associated with skin inflammatory diseases (such as psoriasis and atopic dermatitis), they also play a key role in UV protection and wound healing [66; 67]. In the first, UV exposure causes acute phase responses that stimulate inflammatory factors such as IL-6 and IL-8. The second interleukins, and IL-8 in particular, are one of the most important regulators of wound healing, epithelial regeneration, and angiogenesis [65; 68]. The results obtained for the interleukins production (Figures 6 and 7) showed that, for IL-6 (Figure 6), while all CMC samples had a pro-inflammatory effect upon HaCaT cells, only CMC3 had a stronger pro-inflammatory activity than the LPS control. On the other hand, regarding IL-8 production (Figure 7), the results obtained showed that all CMC samples tested significantly (\(p<0.05\)) reduced IL-8 levels in comparison to the basal control. When analyzing a possible impact of CMC's intrinsic characteristics upon the data obtained, the first major takeaway is that for IL-8 (Figure 7) no factor bears any significant (\(p>0.05\)) weight on the samples' displayed activity. In contrast, data obtained regarding IL-6 (Figure 6) presented a complex pattern of response linked to the DS and crystallinity of the samples. CMC samples' DS appears to influence IL-6 levels, as samples with the lowest DS produced the highest inflammatory response. However, when the DS was above 0.7, sample crystallinity appears to play a significant role, as while both CMC1 and CMC4 have the same DS, CMC4, which has a higher crystallinity index, produced a significantly (\(p<0.05\)) lower inflammatory response. When considering the impact of CMCs upon these specific interleukins' production, no previous works exist that may allow for a direct comparison; however, this does not mean that discussion of the data generated is not possible. When looking into the general effect of CMC on the inflammatory response of cells the existing body of work depicts carboxymethyl cellulose as being, in general, non-inflammatory. [PERSON] and [PERSON] [69], showed that CMC had no pro-inflammatory activity upon HaCaT cells as no increase in the production of TNF-\(\alpha\) was detected. Similarly, [PERSON] and [PERSON] [70] reported CMC as not being pro-inflammatory toward THP-1 cells. Additionally, [PERSON] and [PERSON] [43] showed that cellulose nanofibers reduced IL-6 production in HaCaT cells and, while CMC was not at play here, this interaction shows that, in principle, cellulose-based molecules should not have a pro-inflammatory activity. While all of the previous works support the results here obtained for IL-8, they are contrary to those obtained for IL-6. A possible explanation for this discrepancy may be found in the work of [PERSON] and [PERSON] [50], as the authors showed that the introduction of the carboxymethyl group in cellulose nanofibrils had a pro-inflammatory effect. However, the lack of information regarding CMCs characteristics in these works makes identifying any responsible characteristic or defining any pattern of activity very difficult, and as such, further assays  
Figure 6: IL-6 production in HaCaT cells in the presence of CMC relative to the basal level (control). Different letters represent the statistically significant differences (\(p<0.05\)) found between conditions. Figure 7: IL-8 production in HaCaT cells in the presence of CMC relative to the basal level (control). Different letters represent the statistically significant differences (\(p<0.05\)) found between conditions. are required to better understand CMCs' pro- or anti-inflammatory potential towards HaCaT cells. Last but not least, the increase in IL-6 production observed may be a double-edged sword. On the one hand, IL-6 production by HaCaT has been shown to be able to stimulate fibroblast proliferation; on the other hand, IL-6 production in HaCaT cells has been developed as a non-animal alternative to determine a chemical's skin sensitizing potential [71; 72].