## 4 Discussion
In other studies, \(p\)-coumaric affected macrophage IL-6 secretion only when it was applied after stimulation with LPS [31]. In our investigation, microencapsulated EPP-AF(r) (MPE) increased IL-10 levels without affecting the pro-inflammatory cytokines IL-6 or TNF-\(\alpha\). These activities were not observed for caffe acid, \(p\)-coumaric acid or artepillin C. This profile was similar to that observed for baccharin. Baccharin produced effects similar to those of MPE, also decreasing IL-6 levels. This effect is considered characteristic of an anti-inflammatory profile. In an animal model of acute inflammation, [PERSON] et al. [26] reported anti-inflammatory effects of baccharin due to decreases in pro-inflammatory cytokines (IL-6, TNF-\(\alpha\), and IL-16) and increasedIL-10, in addition to decreasing neutrophil and lymphocyte recruitment to the inflammation site. Baccharin had anti-mutagenic, antioxidant, and neurotrophic effects in vitro [70; 71]. It also had a strong hypoglycemic effect in animal models of type 2 diabetes [72]. Brazilian propolis extracts can have anti-inflammatory, pro-inflammatory, or immunoregulatory effects on the immune system. The effects which predominate generally depend on the extract concentration [73; 74; 75; 76; 77; 78; 79]. In a study by [PERSON] et al. [32], Brazilian green propolis EPP-AF\({}^{\circledR}\) produced an anti-inflammatory effect at lower concentrations (30 and 100 \(\mu\)g/mL) and a cytotoxic effect at a higher concentration (300 \(\mu\)g/mL). [PERSON] et al. [80] reported that in human monocytes, propolis extract produced an anti-inflammatory effect, with increased IL-10 secretion at lower concentrations (5 and 10 \(\mu\)g/mL); however, at higher concentrations (50 and 100 \(\mu\)g/mL), the extract decreased IL-10 secretion and had a fungicidal effect. Our study had some limitations, since it evaluated only three cytokines, with only a single treatment protocol (twenty hours of treatment after two hours of LPS stimulation). Further investigations should be carried out with other models and protocols to better understand how propolis impacts the immune response. However, the data obtained was sufficient to demonstrate that different extract compositions, concentrations, and presentations can affect their effects on immune cells. These three different propolis extract presentations that were produced from the same Brazilian green propolis blend have different physical-chemical characteristics, chemical content and biological properties, which have the potential for use in various types of products, including foods, food supplements, and medicines, as well as hygiene and cosmetic products, with differences and advantages depending on the type of use, physical aspect and formulation compatibilities. Detailed physical-chemical, physical, macro and microscopic aspects of these three presentations are available [53]; this type of information can be useful for selecting the best option for each kind of formulation. Despite the limitations of our study, our results contribute to knowledge about the anti-inflammatory and immunomodolution properties of propolis, confirming its potential for helping to treat chronic inflammatory diseases. Our findings emphasize the importance of an adequate characterization and testing of each type of extract to better understand their immunomodulatory properties and to determine the most appropriate options for specific applications.