If you’ve watched TV lately, chances are you’ve heard a string of letters and numbers that sound more like something from an immunology textbook than a skin-treatment commercial: IL-4, IL-13, IL-17, IL-23. They’re attached to some of the biggest names in eczema and psoriasis treatment, including Dupixent, Ebglyss, Skyrizi and Tremfya. You may recognize the drug names by now, but what those numbers represent and what each treatment actually targets are much less obvious.
The good news is you don’t need an immunology degree to understand the basics. These different “ILs” are part of the immune system’s communication network, and today’s treatments are designed to interrupt specific signals that contribute to inflammation. It’s one reason the treatment landscape for eczema and psoriasis looks so different than it did a decade ago. “These medications have really revolutionized how we treat skin disease and made it possible for improved quality of life for many patients,” says Randolph, NJ dermatologist Cindy Wassef, MD.
Ahead, we break down what IL actually stands for, the specific pathways behind eczema and psoriasis, and why one person’s biologic might not work for someone else.
First, What Does ‘IL’ Actually Mean?
IL stands for interleukin. “These are proteins that act as ‘chemical messengers’ between immune cells to create immune response,” explains Ashburn, VA dermatologist Stephanie Daniel, MD. “Unwanted immune response can lead to unwanted inflammation.”
Different diseases involve different interleukin signaling, which helps explain why eczema, psoriasis and other inflammatory conditions can look and behave so differently. Biologics take advantage of those differences. Dr. Daniel describes them as man-made antibodies that target specific interleukins and shut down that messaging in a very precise way.
Her analogy is one you’ll probably remember the next time an IL number pops up in a commercial: Blocking the signal is “like stopping Paul Revere from calling on the Continental Army to stop the war before it begins.”
That specificity is a major departure from broadly tamping down immune activity. New Haven, CT dermatologist Christopher G. Bunick, MD puts it another way: “Just like our body produces antibodies to defend against infections, scientists have learned how to develop biologics that target very specific drivers of inflammatory skin diseases and neutralize them,” he explains.
The Eczema Pathways
For eczema, the two pathways you’re most likely to hear about are IL-4 and IL-13. “IL-4 and IL-13 are both interleukins involved in propagating atopic dermatitis,” explains Scottsdale, AZ dermatologist Dr. Karan Lal. In simpler terms, they’re immune-system messengers that help keep eczema inflammation going.
Dr. Bunick explains that both signals belong to the same immune response, known as type 2 inflammation. Different eczema drugs target different points within that response: “Dupilumab (Dupixent) targets IL-4 and IL-13, [while] tralokinumab (Adbry) and lebrikizumab (Ebglyss) target IL-13.” All three are FDA-approved for atopic dermatitis.
You may also recognize one drug being advertised for several seemingly unrelated conditions. Dupixent, for example, is used to treat eczema as well as asthma, chronic hives, nasal polyps and eosinophilic esophagitis. “IL-4 is mainly involved in allergic diseases,” explains Dr. Lal. The diagnoses are different, but they share some of the same inflammatory signals, allowing one drug to treat more than one condition.
The Itch Pathway
Then there’s IL-31, a pathway tied directly to something every patient understands: itch. “IL-31 is involved in itch and works on both the skin and the spinal cord,” says Dr. Lal. Although it belongs to the same type 2 inflammatory response as IL-4 and IL-13, it has its own role. Nemluvio (nemolizumab) blocks the IL-31 receptor and is FDA-approved for atopic dermatitis and prurigo nodularis.
The Psoriasis Pathways
With psoriasis, the numbers you’re most likely to hear are IL-17 and IL-23. Dr. Bunick notes that both belong to the same inflammatory network and are involved in psoriasis and psoriatic arthritis. Treatments targeting IL-17 include Bimzelx, Taltz and Cosentyx, while Skyrizi and Tremfya target IL-23.
“IL-23s are newer psoriasis targets,” says Dr. Lal. Most of the IL-23 treatments patients recognize are injectable biologics, but ICOTYDE (icotrokinra) is a once-daily pill that blocks the IL-23 receptor. It gives patients a new way to target the same pathway.
Why Your Friend’s Treatment Might Not Work for You
Even with the same diagnosis, two people can respond very differently to treatment. “Immune-mediated diseases of the skin are rarely purely driven by a single cytokine,” says Dr. Bunick. “There is overlap among the signaling pathways, which is why treatments may have multiple indications, or why one treatment alone may not work as well.”
One person may respond beautifully to an IL-17 or IL-23 inhibitor, while another may need a different target or treatment altogether, which is why finding the right biologic can take some trial and error. It’s also why a psoriasis biologic can stop working or not work well enough, even when it works extremely well for someone else.
How Biologics Have Changed Treatment
Fort Lauderdale, FL dermatologist Dr. Matthew J. Elias calls biologics “life-changing treatments” with “unmatched” efficacy. But having more targeted options also makes choosing the right one increasingly important. “It is so important to reach out to your board-certified dermatologist so they can assist you in picking the right class of drug that will work the best for you,” says Louisville, KY dermatologist Tami Buss Cassis, MD.
As for what comes next, researchers are now studying biologics that can target more than one pathway at once. “This is why we are seeing bi- and tri-specific biologics in development,” says Dr. Bunick. “The idea is this will bring greater disease control to patients.” More IL numbers to decode, yes, but also more precise treatment.
