According to the World Health Organization, over 80 % of the population relies on traditional medicine for primary healthcare, and approximately one third of all traditional herbal medicines are intended to treat inflammatory disorders (Flori et al., 2019). Vegetable oils are an example as they present nutraceutical and functional use. They are used for systemic and skin inflammatory conditions, especially when they are rich in essential and non-essential fatty acids (such as α-linolenic, linoleic, and oleic acid) because these compounds are necessary for fatty acid regulation, cellular composition, and maintenance of epidermal integrity (Vaughn et al., 2018).

Linoleic and α-linolenic acids are polyunsaturated fatty acids (PUFA) classified as essential. In contrast, monounsaturated fatty acids (MUFA), such as oleic acids, are classified as non-essential (Sales-Campos et al., 2013). The benefits of using vegetable oils are linked with these PUFA and MUFA contents.

Several oils from vegetable sources have already been used to control cholesterol, hypertension, and diabetes, demonstrating their properties through clinical trials and experimental studies (Djuricic and Calder, 2021). However, the anti-inflammatory mechanisms of these oils are poorly explained in the literature, which only highlights their nutritional properties. Therefore, this review focuses on oils with higher immunomodulatory ability, emphasizing their performance on immune cells and its consequences.

Natural oils, mainly olive oil (OO), have been used in food for centuries. The beneficial attributes of these oils in the diet allow for the expansion of their use; many studies demonstrate antimicrobial, antioxidant, and anti-inflammatory characteristics, besides traditional benefits for arterial blood pressure, cholesterol-lowering, and diabetes, which makes them an attractive alternative for complementary treatments to the conventional medicine and to a healthy lifestyle (Vaughn et al., 2018). Table 1 summarizes the main health benefits derived from the intake of vegetable oils.

The main characteristic of the Mediterranean diet is the consumption of extra virgin OO as the essential dietary fat. In recent years, many scientific reports have pointed out the nutraceutical and nutritional value of the Mediterranean diet, suggesting that its consumption reduces the incidence of oxidative- and inflammatory-related diseases, such as cardiovascular diseases and cancer (Flori et al., 2019). Indeed, the bio-functional components of OO positively affect genes involved in the pathogenesis of most prevalent age- and lifestyle-related human conditions. OO is a food composed of a significant fat fraction (about 98-99%) represented by oleic acid (55-83%) and other saturated and unsaturated acids (linoleic, palmitic, and stearic acids, 3-21%) and of a minor non-fat fraction (about 1-2%), including a high number of vitamins (α-, β-, γ- and δ- tocopherols), polyphenols (mainly tyrosol, hydroxytyrosol, and oleuropein) and squalene (Flori et al., 2019).

Many reports have demonstrated the beneficial effects of olive oil ingestion, as shown by Widmer et al. (2013), where patients who consumed 30 mL/day for four months improved endothelial functions. The literature proved the OO cardioprotective effect aiming at different targets, improving cardiovascular diseases, such as lowering obesity, increasing antioxidant capacity, diminishing reactive oxygen species (ROS) and inflammatory cytokines, controlling lipid profile levels, decreasing waist circumference and insulin concentration, and the control of blood pressure parameters (Casas et al., 2017). However, OO is contraindicated in skin lesions because it can impair the skin barrier function (Vaughn et al., 2018).

Sunflower oil (SFO) is traditionally used in cooking due to its easy accessibility and health benefits. It is widely preferred in European countries, Mexico, and some places in South America (Petraru et al., 2021). The significant components are linoleic acid (59-65%) and oleic acids (30-70%), representing 48−78% of the total fatty acids profile. However, it also contains palmitic and stearic acids (15% for both fatty acids). SFO is also rich in vitamins, minerals, and phytochemicals such as carotenoids, tocopherols, phenols, and tocotrienols with antioxidant activity. The composition variation depends on the plant species and extraction method (Petraru et al., 2021).

Akrami et al. (2020) demonstrated that seven weeks of SFO ingestion (25 mL/day) significantly increased antioxidant activity. The use of SFO on the skin is widespread, and due to the presence of linoleic acid, SFO can improve the skin barrier function by activating peroxisome proliferator-activated receptor-α (PPAR-a), which regulates keratinocyte proliferation, accelerating skin barrier repair, as demonstrated by in vitro studies and animal models (Vaughn et al., 2018).

Flaxseed/linseed oil (FO) can be considered a medicinal and nutritional product due to its high PUFA content (especially ω-3 and ω-6 groups), lignans, high-quality proteins, fibers, and carbohydrates (Yang et al., 2021). FO is a rich source of essential PUFA, such as linoleic acid (ω-6) and α-linolenic acid (ω-3), which regulate prostaglandin synthesis and enhance wound healing. Also, these essential fatty acids improve the development of the nervous system and reduce cardiovascular disease and cancer. α-linolenic acid is known to lessen the severity and minimize chronic inflammatory and inflammatory bowel disease symptoms. Furthermore, ω-3 fatty acid consumption reduces plasma triglyceride levels and increases HDL-C, improving the lipid profiles (Tanideh et al., 2021).

Chia oil is a preferred and attractive choice for healthy food and cosmetic applications as it has the lowest saturated fatty acid content (palmitic and stearic acid) and an adequate concentration of linoleic acid (18-20%), with a high fatty acid content of α-linolenic acid (55-60%) (Imran et al., 2016). Seeds and biochemical components from Salvia hispanica L. help maintain serum lipid levels, increase the satiety index, and prevent cardiovascular diseases, inflammation, nervous system disorders, and diabetes. A larger supply of α-linolenic acid improves the antioxidant status, fat oxidation capacity, ω-3 long-chain PUFA content, and reduces the activity of fat synthesis biological tissue (Imran et al., 2016).

Other benefits include the capacity to lower blood glucose, waist circumference, and weight in overweight adults and improve pruritic skin and endurance in distance runners (Parker et al., 2018). A topical approach demonstrated the benefits of products containing a chia oil formulation. Five patients with pruritus caused by end-stage renal disease and five healthy volunteers with xerotic pruritus received a topical formulation containing 4% chia oil for eight weeks. The measurement of itching indications, trans epidermal water loss, and skin capacitance demonstrated that chia oil significantly improved skin hydration, lichen simplex chronicus, and prurigo nodularis in all the patients (Jeong et al., 2010).

Immunomodulators have received interest in many areas, mainly because it is possible to target innate and adaptative immunity. Some compounds from plants or food, like polyphenols, can also act as immunomodulators (Yahfoufi et al., 2018), since they have been shown to present anti-inflammatory properties which modulate the immune system. They can abrogate the nuclear factor kappa B (NF-κB), together with the inhibition of the TLR signaling pathway, including phosphatidylinositide 3-kinases/protein kinase B (PI3K/Akt) proteins and mitogen-activated protein kinases (MAPk) complex, which are essentials proteins involved in the process of inflammation (Yahfoufi et al., 2018).

The presence of fatty acids and polyphenols is primarily responsible for the immunomodulation capacity of vegetable oil. The main composition of the oil with immunosuppression properties is composed of oleic (ω-9), linoleic (ω-6), and α-linolenic (ω-3) acids, which are characterized as immunomodulator fatty acids. However, other substances present in lower concentrations, such as phenolic compounds, have been described as substances with properties able to modulate the immune system. So, this section will focus on the immunomodulatory activities of detached fatty acids.

PUFA plays an active role in inflammatory processes (Kwon, 2020), and ω-3 and ω-6 are the two main classes of PUFA which are obtained mainly from plants (canola, soybean, sunflower, and flaxseed) and fish oil. The primary ω-3 fatty acids are α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid, while linoleic acid is the main ω-6 PUFA. These fatty acids are not synthesized in animals, so both fatty acids must be obtained from the diet. Once in the body, α-linolenic acid and linoleic acids can be converted into ω-3 PUFA and ω-6 PUFA, respectively. Still, only α-linolenic acid can be converted into eicosapentaenoic acid and docosahexaenoic acid (Cavalli et al., 2021). ω-3 PUFAs are preferred substrates for desaturase and elongase enzymes involved in eicosanoid biosynthesis (Ruiz-Lopez et al., 2015), favoring the production of anti-inflammatory eicosanoids from the higher intake of α-linolenic acid. Eicosapentaenoic acid and docosahexaenoic acid act as precursors of potent specialized pro-resolving mediators (SPM), such as protectins, resolvins, and maresins (Duvall and Levy, 2016), and their beneficial effects on health are related to the production of less potent pro-inflammatory mediators by preventing the conversion of arachidonic acid to pro-inflammatory eicosanoids or serving as alternative substrates.

The anti-inflammatory effects of α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid are demonstrated in the literature with several studies. Rodríguez-Cruz et al. (2018) showed that supplementation with ω-3 long-chain PUFA in Duchenne muscular dystrophy patients increased eicosapentaenoic acid and docosahexaenoic acid concentrations in erythrocytes from the test group compared to the placebo group after six months. Further, the supplementation promoted a downregulation of the nuclear factor kappa B (NF-kB), interleukin-1 beta (IL-1β), and IL-6 expression compared to the placebo group. In addition, ω-3-PUFA intake decreased the serum levels of IL-1β and IL-6 and increased IL-10. In vitro models demonstrated that eicosapentaenoic acid and docosahexaenoic acid obtained from fish oil could modulate the presence of M2 (cells with anti-inflammatory hallmarks) in obese rat models, reducing the expression of pro-inflammatory genes (IL-6, TNF-α, MCP-1, IL-1β, and iNOS) while increasing the expression of anti-inflammatory genes (arginase-1, IL-10, Mgl-1) (Akinkuolie et al., 2011). Cell experiments showed that α-linoleic acid (10-60μM) inhibited the pro-inflammatory phenotype of M1-like macrophages and reduced the expression of IL-6, TNF-α, MCP-1, and IL-1β in LPS-stimulated human THP-1 cells (Pauls et al., 2018). Also, α-linoleic acid (10-200 mg/kg) improved LPS-induced cystitis in mice through the reduction in the expression of IL-6, TNF-α, COX-2, PLA2, and iNOS, inhibiting the activation of the NF-κB signaling pathway (Ok et al., 2020).

Hogenkamp et al. (2011) demonstrated the immunomodulation promoted by PUFA in two murine models: influenza vaccine in C7BL/6 mice and experimental allergy in BALB/c mice. The animals were fed vegetable oils (SFO and linseed), fish oil (salmon), and beef fat. The animals that ingested oil from the marine source had the best results in influenza immunization and showed fewer allergy symptoms. Although the linseed had similar concentrations of ω-3 PUFA to fish oil, the last had higher eicosapentaenoic acid and docosahexaenoic acid amounts. Using Th1 (C57BL/6) and Th2 (BALB/c), models demonstrated that ω-3 PUFA presents immunomodulating characteristics.

Oleic acid is an ω-9 monounsaturated fatty acid (MUFA) present in OO and is responsible for the beneficial effects observed in this oil (Casas et al., 2017). Oleic acid has been demonstrated to possess immunomodulatory ability, acting on T lymphocytes, neutrophils, and macrophages. The action on neutrophils has a dual role, depending on the model (stimulated or not stimulated). The oleic acid reduced cell migration in an in vitro LPS-induced model (Reyes-Quiroz et al., 2014). However, when applied isolated, oleic acid showed stimulatory characteristics on neutrophils, increasing ROS production in human and rat cells under in vitro assays (Carrillo et al., 2011). It also increased the release of vascular endothelial growth factor-α (VEGF) and IL-1β in rat neutrophils (Carrillo et al., 2011). The oleic acid action on macrophages seems to have an anti-inflammatory attribute once a diet rich in this MUFA elevates the levels of M2 macrophages (cells with anti-inflammatory hallmarks) in the adipose tissue of mice and increases the levels of M2 markers (CD206, MGL1, and ARG1) in RAW 264.7 macrophages in vitro (Camell and Smith 2013).

The action of poly and monounsaturated fatty acids could occur in human microbiota, indirectly reaching the immune system. A review showed that in addition to the biological activities, ω-3 PUFAs seem to impact the gut microbiome, mainly by three effects: altering the diversity and quantity of gut microorganisms, modulating the concentration of pro-inflammatory cytokines such as intereleukin-17, and altering the levels of short-chain fatty acids (SCFA) (Djuricic and Calder, 2022). This effect was demonstrated previously by Watson et al. (2018), who found that that ω-3 PUFA may be capable of interacting with the gut microbiota and changing the SCFA levels to modulate immune functions. In a randomized controlled trial, healthy participants with ω-3 PUFA supplementation resulted in increased quantities of Bifidobacterium, Roseburia, and Lactobacillus, known for their immunoregulatory properties. The decrease in intestinal bacteria diversity also affects gut dysbiosis, which are associated with neuroinflammation. So, a diet enriched with ω-3 PUFA can provoke an anti-inflammatory shift, leading to the prevention or amelioration of neuroinflammation (Kerman et al., 2024).

As explained above, vegetable oils are an essential source of ω-3 (α-linoleic acid) and ω-6 (linoleic acid) PUFAs, and ω-9 MUFA (oleic acid), all of which have prodigious immunomodulation activities. The various effects of vegetable oils on the immune system are explained in this section and summarized in Figure 1.

Different studies support and describe the beneficial role of OO in the prevention of cardiovascular disease and degenerative diseases, together with breast, skin, and colon cancers, as well as the benefits in the prevention and reduction of hypercholesterolemia, lipoprotein concentrations, atherosclerosis, hypertension, thrombotic risk, oxidation, oxidative stress, obesity, and type 2 diabetes (Cicerale et al., 2012). These functions and immunosuppressive activity are attributed to oleic acid, the most predominant fatty acid in the OO formulation.

Studies have shown that ingesting extra-virgin OO could decrease inflammation markers such as IL-6 and C-reactive protein, demonstrating that consuming 50 mL daily for two or three weeks diminished these parameters (Camargo et al., 2010). Widmer et al. (2013) described an improvement in endothelial function in a group ingesting 30 mL of pure extra-virgin OO and another group receiving a 30-mL extra-virgin OO supplement (epigallocatechin 3-gallate), with a significant reduction in inflammatory parameters and oxidative stress only in the group consuming the pure extra-virgin OO.

Puertollano et al. (2004) demonstrated that an OO-enriched diet could increase the levels IL-4 in mice sera after a challenge with Listeria monocytogenes, an intracellular bacterium. An augment in IL-4 activates the Th2 pathway response, showing an immunosuppressive effect of the OO ingestion, promoting better control of inflammation.

The beneficial immunosuppressive effects of OO were also observed in an autoimmune Systemic Lupus Erythematosus (SLE) animal model (Aparicio-Soto et al., 2016). SLE mouse models were fed with SFO or OO. Animals treated with the OO diet significantly reduced the characteristic renal damage and decreased MMP-3 in the serum while decreasing PGE2 in the kidney. The production of the pro-inflammatory cytokines TNF-α, IL-17, and IL-6 in LPS-stimulated splenocytes was diminished compared to the SFO group. Further, the Nrf-2 and HO-1 protein expressions were up-regulated in those mice fed with extra-virgin OO, drastically facilitating the activation of JAK/STAT, MAPK, and NF-κB pathways. OO seems to possess anti-inflammatory effects, beneficiating the control of the exacerbated inflammation.

Chia seeds are rich in antioxidant properties, and the originated oil is a natural source of ω-3-fatty-acids and α-linoleic acid, containing α-linoleic, linoleic, and oleic acid (Kulczynski et al., 2019). Using a rheumatoid arthritis rat model under obesity induced by a high-fat diet, Mohamed et al. (2020) showed that the oral intake of 300 mg of chia oil promoted a decrease in swelling, decreasing the volume of inflammation, as well as TNF-α levels in the plasma.

Chia oil is also associated with anti-inflammatory properties, as Cavalli et al. (2021), demonstrated. Compared to the non-treated animals, chia oil delayed the beginning of animal symptoms under an experimental model of multiple sclerosis known as EAE (experimental autoimmune encephalomyelitis). In croton-oil and carrageenan-induced inflammatory models, such as paw and ear edemas, the intake of chia oil, followed by the administration of a pro-inflammatory stimulus, promoted a reduction in several markers, demonstrating anti-edematogenic and anti-hyperalgesic effects. However, under nervous inflammation induced by carrageenan, the treatment with chia oil decreased the production of IL-6 and COX-2, promoting a reduction in inflammation.

The effects of SFO on inflammation have demonstrated dubious results. Despite the presence of linoleic acid (an ω-6 PUFA) in its composition, Masi et al. (2012) have shown that the supplementation with SFO in high-fat diet-induced obese mice did not decrease the inflammatory status, as it did not decrease IL-6 and TNF-α from peritoneal macrophages and the adipose tissue; however, supplementation with SFO improved the serum lipid profile in treated animals. In another study, rats were submitted to a higher cholesterol diet and supplemented with SFO or phenolic-enriched SFO. The concentration of E-selectin, VCAM-1, and ICAM-1 in the animals’ aortas were evaluated and indicated that SFO or enriched SFO did not change the status of these molecules. However, when oleic acid was added to SFO, it improved its anti-inflammatory capacity, reverting the presence of E-selectin, VCAM-1, and ICAM-1 (Katsarou et al., 2015).

Also, mice under lymph node inflammation induced by LPS injection received chow supplemented with 20% SFO. The supplementation promoted an increase in dendritic cells in the adipose tissue of the animals compared to the animals that received plain chow (Mattacks et al., 2004). SFO has a more pronounced anti-inflammatory activity on topical use, with studies demonstrating benefits to wound healing (Lania et al., 2019; Vaughn et al., 2018).

Linseed (flaxseed) oil contains similar α-linoleic acid concentrations to fish oil and could be a vegetable source of ω-3 PUFA. The anti-inflammatory ability of linseed oil is evident, demonstrated experimentally and in clinical trials, as shown in high fat-diet (HFD) rats, with a reduction in the expression of IL-6 and an increase in IL-10 (Jordão Candido et al., 2019). In another animal model of HFD-induced Δ-6 desaturase knockout mice (preventing the metabolism of α-linoleic acid), Monteiro et al. (2013) confirmed that flaxseed oil containing α-linoleic acid could directly inhibit fat accumulation and inflammation response, demonstrating no need to be converted to EPA or DHA to be effective.

Using a tumor animal model with a C57BL/6 mouse, a research group showed that the treatment with flaxseed oil orally alone or together with cisplatin for 15 days did promote the regulation and balance of Th1/Th2 response, as the levels of IL-4 were reduced, but the IFN-γ was increased, compared to the mice treated only with cisplatin. Still, treating flaxseed oil and cisplatin promoted increased CD8+ T cells in the spleen (Deshpande et al., 2019).

Bashir et al. (2019) verified that the treatment of flaxseed oil in insulin resistance induced by high-fat resulted in a decrease in the expression of NF-κB, IFN-γ, TNF-α, IL-12 and IL-1β in the adipose tissue macrophages (ATM). While it presented an increase in the arginase-1 expression and IL-4 concentration, flaxseed oil still promoted a suppression in immune cell migration to the adipose tissue.

The importance of vegetable oils in the population’s diet worldwide is proven. In addition, these oils have been shown to benefit consumers, such as the balance of the lipid profile, cardiovascular improvements and decrease in blood pressure, along with healing effects when used topically. Most of these benefits come from the immunomodulatory effects of vegetable oils, mainly the anti-inflammatory activities triggered by the unsaturated fatty acids present in these oils. However, despite the large number of clinical studies available on the prevention of cardiovascular events, these studies did not conclude categorically the full therapeutic efficacy of PUFAs and MUFA. Thus, it is essential to characterize and understand the effects of vegetable oils on the immune system, especially those with high concentrations of PUFA and MUFA.