The Science of Skin Inflammation
Inflammation occurs when one of the pathways discussed below is activated. It is a complicated process because all of the pathways influence each other on, causing a domino effect. This is a brief discussion of the science of what causes skin inflammation.
This material is adapted from Anti-inflammatory Ingredients in Ch. 38 of Baumann’s Cosmetic Dermatology (McGraw Hill 2022)
Eicosanoids in Skin Inflammation
Phospholipids found in the cell membrane are hydrolyzed by phospholipase A2 (PLA2), releasing free arachidonic acid (AA). This fatty acid is the primary precursor of eicosanoids. Eicosanoids are mediators of inflammation. Types of eicosanoids are:
Prostaglandins
Thromboxanes
Leukotrienes
Prostacyclins
There are two different pathways in the synthesis of eicosanoids from AA:
Cyclooxygenase (COX) pathway: Prostaglandins, thromboxanes, and prostacyclins
are synthesized via the cyclooxygenase pathway. Two cyclooxygenases have been identified: COX-1 and COX-2. COX-1 is ubiquitous. COX- 2 is induced in response to inflammatory stimuli.
Lipoxygenase pathway: Lipoxygenase enzymes can act on AA to form hydroperoxyeicosatetraenoic (HPETE) acids (5-HPETE, 12-HPETE, and 15-HPETE). HPETEs are then rapidly reduced to hydroxylated derivatives (HETEs), LTs, or lipoxins.
Cytokines in Skin Inflammation
Cytokines are signals that cells produce. Cytokines that play a role in inflammation are produced by various cell types, but the most important sources are the immune cells: macrophages and monocytes found in the inflammatory areas. See Table “Inflammation-Associated Cytokines” so see which cytokines play a major role in inflammation.
As seen in the table, numerous types of cytokines play a role in skin inflammation. Two of these orchestrate inflammation: interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α). These two cytokines induce the production of lipid mediators, proteases, and free radicals. The cytokines interferon-γ (INF-γ) and granulocyte colony-stimulating factor (G-CSF) amplify the inflammatory response by increasing the production of IL-1 and TNF-α by macrophages.
Chemokines
Chemokines (chemotactic cytokines) are small proteins that direct the movement of circulating white blood cells to areas of inflamed skin.
Mast Cells in Skin Inflammation
Mast cells are activated to release histamine by binding the immunoglobulin E (IgE) or by physical stimuli (e.g., heat, cold, and sunlight), macrophage-derived cytokines, bacterial toxins, venoms, trauma, and the presence of allergens.
Skin Allergies
When a mast cell armed with IgE antibodies is re-exposed to an allergen, multiple responses occur, leading eventually to the release of various potent mediators responsible for the clinical expression of immediate inflammatory-hypersensitivity reactions that is commonly called “an allergic reaction” or “hives”. In the first step of this sequence, antigens bind to the IgE antibodies previously attached to the mast cells. The bridging of IgE molecules with the underlying IgE-Fc receptors activates signal transduction pathways that will translate into three outcomes:
1) Degranulation, with the secretion of preformed mediators like vasoactive amines (e.g., histamine), neutral proteases (e.g., chymase, tryptase, hydrolase), and proteoglycans (e.g., heparin, chondroitin sulfate);
2) De novo synthesis of pro-inflammatory lipid mediators (i.e., LTs C4, D4, and B4, and PG D2)
3) Synthesis and secretion of cytokines (i.e., TNF-α, IL-1, IL-3, IL-4, IL-5, IL-6, and GM-CSF), as well as chemokines, such as macrophage inflammatory protein (MIP)-1α and MIP-1β.
Histamine and Skin Inflammation
Histamine is stored in mast cells. When mast cells degranulate, they release histamine. When histamine binds the H1-receptor, cytokines and lysosomal enzymes from macrophages are released and cell-adhesion molecules are expressed which influences the activity of basophils, eosinophils, and fibroblasts. Both the H1- and H3-receptors play a role in the itching felt during a skin allergy.
Free Radicals and Skin Inflammation
White blood cells release oxygen-derived free radicals after exposure to challenges such as microbes, chemokines, or immune complexes. Free radicals cause the expression of chemokines, cytokines, and endothelial leukocyte adhesion molecules, amplifying the inflammatory cascade and making inflammation worse. High levels of free radical cause cell damage triggering more inflammation and destruction of the extracellular matrix and loss of hyaluronic acid, collagen, and elastin.
Kinins in Skin Inflammation
The kinin-kallikrein system is a network of circulating proteins that affect inflammation, blood pressure control, coagulation, and pain. Kinins [bradykinin (BK) and kallidin (KD)] are polypeptides produced from kininogen and broken down by kininases. They are rapidly generated after tissue injury and they affect the inflammatory process by increasing arachidonic acid release and increasing eicosanoid production and activating nuclear factor-κB (NF-κB), further contributing to the inflammatory response. Kinins also induce pain.
DQH Can I use salicylic acid first and then vitamin C?
It’s easy to create a skincare routine, but knowing how to use it is another thing entirely. In most cases, if you’re not getting the desired skin results, it could be due to the layering of conflicting ingredients. So, is it possible that salicylic acid and vitamin C are such ingredients? Or are these active ingredients the duo that’s been missing from your skincare routine? If you want answers, stick around because today we are going to explain the benefits of salicylic acid and vitamin C and how they can be used in your daily life.
What are the benefits of salicylic acid for skin?
Salicylic acid is one of the most commonly used beta hydroxy acids and is favored by many people with oily, acne-prone skin. This acid is derived from willow bark, and unlike its water-soluble relatives (called alpha-hydroxy acids), salicylic acid is oil-soluble, which means it can penetrate deeper into the lower layers of the skin. Once it reaches the lower layers, it can help unclog pores of excess sebum, dirt, bacteria, debris, and impurities. This results in clearer skin tones and greater definition.
Not only does salicylic acid benefit the underlying layers, but the outer surface of the skin benefits as well. When applied to the skin, salicylic acid removes the buildup of dead skin cells. This is accomplished by breaking the bonds that hold dead cells to the surface. Over time, this can cause the complexion to look dull and prone to acne, blackheads, and other blemishes.
If you’d like to learn more about salicylic acid and how it can improve your skin, check out this dedicated blog post from a beauty insider.
What are the benefits of vitamin C for skin?
Vitamin C is considered one of the most powerful antioxidants, which means it is very effective at fighting free radicals and preventing them from causing further skin damage. Examples of free radicals include pollution, central heating, UV rays and harsh climate. They attack proteins, fats and cell membranes as soon as they come into contact with the skin, causing signs of premature aging such as fine lines and wrinkles as well as hyperpigmentation, flaky patches of skin and loss of elasticity.
Many people usually prefer to use vitamin C in their morning routine as this ingredient gives the complexion a radiant glow. You’ll also find that vitamin C can target areas of hyperpigmentation, plumping the skin and reducing the appearance of fine lines and wrinkles.
The thing about vitamin C is that there are a lot of outdated studies going back to the 1950s that describe vitamin C as an unstable skin component. Thanks to improvements in modern technology, this is no longer the case as all products now contain a stable form of vitamin C.
Visit The Beauty Insider to learn more about vitamin C. So please check out our blog post.
Can I use salicylic acid first and then vitamin C?
Yes, you absolutely can. In fact, it’s thought that using salicylic acid before using vitamin C ensures it penetrates faster and works faster.
This is an efficient way to utilize two power sources, and the reason has to do with pH. For example, the skin’s natural pH is about 4.7, making it slightly acidic. Salicylic acid and vitamin C are also both acidic, and you’ll find that vitamin C is absorbed quickly into the skin. Therefore, using salicylic acid beforehand can increase the acidity of the skin and allow vitamin C to penetrate into the skin faster.
While this is considered an effective way to combine two powerful ingredients, you need to be aware of your skin type and how it reacts to certain active ingredients. Even people with perfect, normal skin can experience skin sensitivity and irritation. Therefore, always consult a doctor or dermatologist before using any new products on your skin.
It’s also important to follow skin application rules. In this case, you need to use the product correctly to ensure you get the best results for your skin. If you’re not sure what I mean, the basic rule for skin is to start with the thinnest consistency and work your way up to the thickest consistency. This prevents a barrier from forming on the surface, preventing other active ingredients from penetrating the skin.
Can I use salicylic acid at night and vitamin C in the morning?
Yes, absolutely, this is considered the most effective way to get returns without any adverse side effects. This is because there is enough time between applications to ensure that the skin’s pH levels return to balance.
You’ll also find that Vitamin C is rich in antioxidants and is perfect for use in the morning to ensure your skin is protected and looking its healthiest. Due to the small size of salicylic acid molecules, it is an acid that is able to reach the deepest parts of the skin. While this is effective at keeping skin clear, it also increases the risk of irritation and photosensitivity. Therefore, many people prefer to use powerful BHAs in their evening routine without exposure to UV rays, pollution, or harsh weather.
Warning: If you avoid using sunscreen every day, none of these ingredients will do what your skin needs. The combination of chemical peels and powerful ingredients increases the risk of further damage to the skin’s surface. Use SPF 50 every day to keep your skin protected and your lipid barrier healthy, even on cloudy days, keeping your skin in top condition.
