How Skin Inflammation Starts and How You Can Treat It

The Science of Skin Inflammation: A Comprehensive Overview

Skin inflammation is a complex, multi-step biological process triggered by a wide array of stimuli ranging from pathogens and allergens to environmental damage and internal imbalances.

It plays a dual role in the human body: on one hand, it is a defense mechanism vital to healing; on the other hand, chronic or dysregulated inflammation can be damaging and contributes to numerous skin disorders.

This comprehensive guide provides a scientific overview of the inflammatory mechanisms that operate within the skin.

It draws from foundational content adapted from Chapter 38 of Baumann’s Cosmetic Dermatology (McGraw Hill, 2022), elaborating on the molecular and cellular players that initiate and propagate inflammation in response to both external insults and internal triggers.

What Is Skin Inflammation?

Inflammation is the body’s protective response to harmful stimuli, such as pathogens, damaged cells, toxic compounds, or physical injury.

It involves immune cells, blood vessels, and molecular mediators. In the skin, inflammation is characterized by redness, swelling, warmth, pain, and often itching or dysfunction of the skin barrier. While acute inflammation is beneficial for healing, chronic inflammation can cause long-term tissue damage, pigmentation issues, premature aging, and disease progression.

Skin inflammation can be initiated through multiple interconnected pathways, each influencing and amplifying the others in a domino-like fashion.

The following sections explore the most important mechanisms involved.

1. Eicosanoids and the Arachidonic Acid Pathway

Arachidonic Acid (AA) Metabolism

One of the earliest molecular signals in skin inflammation arises from the cell membrane, where phospholipase A2 (PLA2) acts on membrane phospholipids to release arachidonic acid (AA).

This omega-6 polyunsaturated fatty acid serves as the precursor to a group of potent signaling molecules known as eicosanoids, which include:

Prostaglandins (PGs)

Thromboxanes (TXs)

Leukotrienes (LTs)

Prostacyclins

These compounds have diverse and powerful biological effects, especially in inflammation and immunity. Two main enzymatic pathways convert AA into these mediators:

Cyclooxygenase (COX) Pathway

This pathway produces prostaglandins, thromboxanes, and prostacyclins. Two main cyclooxygenase enzymes are involved:

COX-1: A constitutive enzyme expressed in most tissues. It maintains homeostatic functions like gastric protection and platelet aggregation.

COX-2: An inducible enzyme that is rapidly upregulated in response to pro-inflammatory stimuli such as cytokines and bacterial endotoxins.

Its products play a central role in inflammation and pain.

COX-derived eicosanoids mediate vasodilation, increased vascular permeability, and pain—all hallmarks of inflammation.

Lipoxygenase (LOX) Pathway

The LOX pathway transforms AA into hydroperoxyeicosatetraenoic acids (HPETEs)—such as 5-HPETE, 12-HPETE, and 15-HPETE—which are further reduced to hydroxyeicosatetraenoic acids (HETEs), leukotrienes, and lipoxins.

Leukotrienes (especially LTB4) are highly chemotactic and attract immune cells to the site of injury.

Lipoxins help resolve inflammation, acting as a counterbalance to leukotrienes.

These lipid mediators are essential players in orchestrating immune responses in the skin.

2. Cytokines: The Molecular Messengers of Inflammation

Cytokines are small signaling proteins secreted by immune and skin cells to communicate with one another.

In inflammatory skin conditions, cytokines are primarily released by immune cells such as macrophages and monocytes, though keratinocytes and fibroblasts can also produce them.

Key Pro-Inflammatory Cytokines

Interleukin-1 (IL-1) and Tumor Necrosis Factor-alpha (TNF-α) are major orchestrators of the inflammatory cascade. They stimulate the release of:

Proteases (which degrade tissue),

Reactive oxygen species (ROS),

Other cytokines and eicosanoids.

Interferon-gamma (IFN-γ) and Granulocyte Colony-Stimulating Factor (G-CSF) enhance the production of IL-1 and TNF-α, amplifying inflammation.

These cytokines are involved in many skin conditions, including acne, psoriasis, eczema, and allergic reactions.

3. Chemokines: The Navigators of Immune Cells

Chemokines are a specialized subset of cytokines with chemotactic properties. They guide immune cells—such as neutrophils, eosinophils, and lymphocytes—to sites of tissue damage or infection.

During skin inflammation, chemokines:

Recruit immune cells from the bloodstream,

Direct them toward the inflamed tissue,

Play a role in both initiating and resolving inflammation.

Persistent overproduction of chemokines can result in chronic inflammatory states and tissue damage.

4. Mast Cells and Histamine in Skin Inflammation

Mast cells are resident immune cells in the skin and other tissues, best known for their role in allergic responses. They contain granules rich in histamine and other inflammatory mediators.

Activation Triggers

Mast cells can be activated through several mechanisms:

IgE binding and crosslinking upon exposure to allergens,

Physical stimuli such as heat, cold, and UV radiation,

Microbial toxins, trauma, and cytokines.

Outcomes of Activation

Upon activation, mast cells undergo degranulation, releasing:

Pre-formed mediators: histamine, tryptase, chymase, and heparin.

Newly synthesized lipid mediators: such as leukotrienes (C4, D4, B4) and prostaglandin D2.

Pro-inflammatory cytokines: including TNF-α, IL-4, IL-5, IL-6, and GM-CSF.

These substances cause itching, vasodilation, increased vascular permeability, and recruitment of other immune cells, culminating in the hallmark symptoms of skin allergies like urticaria (hives).

5. Histamine’s Role in Allergic Skin Reactions

Histamine, stored in mast cells, is a key mediator of allergic inflammation. When it binds to specific histamine receptors (especially H1 and H3 receptors), it can:

Promote the release of additional cytokines,

Attract basophils and eosinophils,

Stimulate fibroblasts to remodel tissue,

Cause the characteristic itching of allergic skin diseases.

Histamine’s action on the H1 receptor is primarily responsible for the itching, redness, and swelling associated with allergic reactions.

6. Free Radicals: The Amplifiers of Skin Damage

During inflammation, white blood cells such as neutrophils and macrophages generate reactive oxygen species (ROS) or free radicals as part of their defense against microbes.

However, excessive production of ROS can damage healthy skin cells.

Consequences of ROS in Skin Inflammation:

Induction of further chemokines and cytokines,

Expression of endothelial adhesion molecules, enhancing immune cell infiltration,

Breakdown of extracellular matrix components like collagen, elastin, and hyaluronic acid,

Acceleration of skin aging and pigmentation changes.

Antioxidants in skincare can help mitigate these effects by neutralizing ROS and restoring redox balance.

7. Kinins and the Kallikrein-Kinin System

Kinins such as bradykinin (BK) and kallidin (KD) are peptide mediators that are rapidly formed after skin injury through activation of the kallikrein-kinin system.

These molecules have a range of effects on skin inflammation:

Increase vascular permeability,

Stimulate the release of arachidonic acid,

Promote eicosanoid synthesis,

Activate NF-κB, a transcription factor that regulates the expression of pro-inflammatory genes.

Kinins are also involved in the sensation of pain and itching, making them crucial targets for anti-inflammatory therapies.

Final Thoughts: Implications for Skin Health and Treatment

The process of skin inflammation is intricate and involves multiple overlapping pathways that can either promote healing or lead to chronic skin conditions if not properly regulated.

Understanding the molecular science behind inflammation offers a roadmap for targeted treatment and prevention.

Modern dermatology increasingly focuses on anti-inflammatory skincare that targets:

COX and LOX pathways (via botanicals or NSAIDs),

Cytokine signaling (via immunomodulators),

Mast cell stabilization (via antihistamines),

Antioxidant protection (via vitamin C, E, niacinamide),

Kinin inhibition (via emerging peptides and topical agents).

With ongoing research, more refined therapies are being developed to manage inflammation without suppressing the skin’s natural defenses.

DQH Knowledge drop: In your 20s, your skin cell turnover decreases. (Cell turnover is a key component in keeping your skin youthful.) You know what else slows down? Your collagen production. Starting in your 20s, collagen decreases by about 1 percent per year. Should you want to prevent fine lines and wrinkles, start by eliminating behaviors that contribute to premature aging. “If it’s bad for you, it’s bad for your skin,” says dermatologist Michel Somenek. “Cigarette smoking reduces blood flow to the skin and causes premature wrinkling and a dull skin texture. Making the repeated pursed motion to inhale can also cause smoker’s lines. Alcohol and recreational drugs are toxins for the skin that damage its cellular structure and DNA,” Somenek tells us. “The faster you eliminate vices while you are young, the better chance your skin and body have to recuperate.” Also, adopting an anti-aging routine in your 20s is key. After all, the best offense is a good defense. We spoke to Somenek and experts Joshua Ross and Audrey Kunin to find out more. Keep reading for the best anti-aging products for your 20s, according to skincare professionals. Sunscreen “We all know that the sun is the number one cause of skin aging and starting the prevention in your 20s is very important,” Ross says. “The majority of your sun damage won’t start to appear until you’re in your 30s, so don’t wait until you see it surface or you’ll be behind the curve. Stay ahead of it with a good-quality zinc-based sunscreen worn daily.” Farmacy Green Defense Daily Mineral Sunscreen An invisible sunscreen with SPF 30, plus botanical extracts meant to protect skin with tons of antioxidants. Bonus: It’s clean and fine to use under makeup. Bareminerals Complexion Rescue™ Tinted Moisturizer Broad Spectrum SPF 30 Although we recommend you use your SPF and moisturizer separately, we also understand moments when you don’t have time or energy for that extra step. For those times, this bareMinerals moisturizer is a great thing to have on hand. Vitamin C Serum “A great introduction to anti-aging is to start with a vitamin C serum in your morning skincare routine,” Ross says. “It’s a powerful antioxidant that will neutralize free radicals and brighten the skin.” He adds that it’s a great way to counteract the effects of the sun’s harmful rays, which, as previously mentioned, are among the biggest causes of premature aging. Drunk Elephant C-Firma™ Vitamin C Day Serum The Drunk Elephant C-Firma is a lightweight serum that promises to give skin a glow by combining the brightening powers of vitamin C with ferulic acid, l-ascorbic acid, and vitamin E. The included sodium hyaluronate is meant to replace hydration loss, so you shouldn’t have to deal with any irritation. Sunday Riley C.E.O. Rapid Flash Brightening Serum This potent serum is jam-packed with vitamin C (15 percent, to be exact), which means it’s a potential superstar at both brightening skin and dousing it in antioxidants. Peptides Using peptides on your skin has many benefits, says Somenek. “The skin barrier is what defends the body against pollution, UV rays, bacteria, and toxins. It can be damaged by several everyday factors. Using topical peptides aids in building a stronger barrier,” he says. “Peptides comprise elastic fibers, which are a type of protein. These fibers help to make skin appear taut and firm. Peptides can also help repair damaged skin, relieve inflammation, and even out skin tone. Some peptides can kill acne-causing bacteria that is common in 20-somethings.” Kunin agrees, saying, “Peptides are an excellent entry point for supporting collagen.” She recommends looking for face and eye treatments that contain these collagen-boosting powerhouses. Charlotte Tilbury Magic Eye Rescue Cream This Charlotte Tilbury super-emollient eye cream has a base of coconut oil and shea butter (read: it’s incredibly hydrating). Botanicals plus peptides are meant to help reduce dark circles and boost collagen, respectively. This creamy moisturizer serves up potent collagen-boosting peptides and pycnogenol, and antioxidant-rich vitamin C. “Instead of sitting on top of the skin, peptides penetrate the outer layer so they go deep. The ‘signals’ they send tell the cells to produce elastin and collagen, which are needed for youthful-looking skin,” explains Somenek. At-Home Peel Pads Remember that skin cell turnover fiasco we talked about earlier? One way to help support it is by exfoliating. “Exfoliation is important to help keep skin fresh and luminous,” Kunin says. She recommends using at-home peel pads as an easy and effective way to exfoliate. “The goal in your 20s is to fight the slowing pace of cell turnover. It is wise to use products that gently exfoliate, yet still remove oil and other impurities. Products that have Alpha Hydroxy Acids (AHA) or Beta Hydroxy Acids (BHA) are a good choice.” According to Somenek, you should only exfoliate two to three times a week. “People of all ages are guilty of over-exfoliating and that can be too much of a good thing,” he says. Dermadoctor Kakadu C Intensive Vitamin C Peel Pad A few swipes of this Derma Doctor powerful peel pad promise to leave your skin glowing and smooth, thanks to the seven (yes, seven) types of chemical exfoliants, including AHA and BHA. It also contains vitamin C via Kakadu plum extract for added brightening and antioxidant protection. KEY INGREDIENTS Kakadu plum extract is sourced from the Kakadu plum, a fruit grown in northern Australia. It contains vitamin C, which restores the skin’s natural barrier, increases collagen production, and soothes irritation. Dr. Dennis Gross Skincare Alpha Beta® Universal Daily Peel Pads These are the gold standard of peel pads, with a cult following and over 900 five-star reviews on Sephora. They’re easy to use and contain a blend of anti-aging exfoliating acids. Emollient Night Cream “In your 20s, you need to start upping the hydration in your skincare routine. You may have been cautious of over-moisturizing because of acne in your teens, but as you enter your 20s, your skin transitions and becomes drier,” Ross says. “I recommend an emollient night cream added into your evening skincare regimen.” “Twenty-somethings need to make sure that they are not using creams that will clog their pores and cause excess oil production,” says Somenek. Opt for non-comedogenic products. Cerave Skin Renewing Night Cream One great choice is the CeraVe Skin Renewing Night Cream, which is a non-comedogenic night cream that leaves skin soft and glowy. It combines the moisturizing powers of ceramides and hyaluronic acid. RoC Retinol Correxion Max Hydration Creme “The best night cream ingredients contain retinol, benzoyl peroxide, and/or salicylic acid or hyaluronic acid. The goal is to moisturize, yet remove excess oil,” says Somenek. This Roc Retinol Correxion cream fits the bill as it contains both hyaluronic acid and retinol so it promises to moisturize while also being non-comedogenic.

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