IL13

IL-13 is an immune system protein that can stimulate the release of antibodies and compromise the skin barrier. [R].

IL-13 is generally an anti-inflammatory cytokine. It blocks the production of proinflammatory cytokines and interferon-gamma (IFN-γ). IL-13 is mostly produced by Th2 cells [R, R].

Variants of IL13 may play a role in allergies and alopecia areata, as well as breast cancer and atopic dermatitis. Lifestyle and supplement modifications may counteract the effects of these variants by decreasing IL-13 production [R, R, R].

One IL13 variant, rs20541-A, is associated with lower rates of acute lung failure arising from ARDS, a often fatal complication of respiratory diseases, but may also play a role in allergic reactions.

Cytokine (PubMed:8096327, PubMed:8097324). Inhibits inflammatory cytokine production (PubMed:8096327). Synergizes with IL2 in regulating interferon-gamma synthesis (PubMed:8096327). May be critical in regulating inflammatory and immune responses (PubMed:8096327, PubMed:8097324). Positively regulates IL31RA expression in macrophages.

IL13, Allergies, and Alopecia Areata

The IL13 gene codes for interleukin 13 (IL-13), a protein released by type 2 immune response (Th2) cells. Along with IL-4, it fights pathogens and other outside threats that don’t enter our cells but stay in the fluids (humor=fluid). IL-13 and IL-4 have similar roles and health effects [R, R].

On the one hand, IL-13 can prevent excessive inflammation in response to microbial infections. On the other, it plays a crucial role in allergic asthma and airway hypersensitivity, which are Th2-dominant conditions . IL-13 and IL-4 also enable robust defense against worms and other parasitic infections [R, R, R, R, R].

Type 2 immunity, driven by the Th2 cells, is often regarded as anti-inflammatory, but it can also trigger inflammation under specific conditions. It’s responsible for allergic reactions and the rejection of foreign bodies, including transplants [R, R].

While many scientists consider elevated Th2 activity to underlie a number of allergic diseases, its role in autoimmune diseases such as alopecia areata (spot baldness) is not well understood [R, R, R].

More recently, scientists have suggested that patients with allergies may be more predisposed to developing certain autoimmune disorders, including alopecia areata [R]. 

Indeed, IL-13 is able to stimulate the release of a type of antibody called IgE from immune system cells. The release of IgE antibodies is an early step in the progression of allergic reactions, and elevated IgE levels have been reported in individuals with alopecia areata [R, R].

IL-13 might also inhibit the production of a protein called filament aggregating protein (filaggrin). Filaggrin helps provide structure to the outermost layer of the skin by binding together a type of fibrous protein called keratin. In this manner, filaggrin is able to maintain a skin barrier that can protect against allergens (allergy-causing substances), bacteria, and viruses [R, R, R]. 

Skin barrier integrity may be similarly essential for the prevention of alopecia areata, as dysfunctional filaggrin has been linked to more severe cases of this disorder [R].

Variants of IL13 have been associated with  allergic diseases and alopecia areata. These variants may increase the production of IL-13, resulting in increased IgE antibody release and decreased production of filaggrin. This may, in turn, promote allergic reactions that have the potential to lead to autoimmunity [R, R, R, R, R, R, R, R]. 

Elevated IL-13 may also decrease the production of filaggrin. Lack of filaggrin would compromise the structure of the outermost skin layer, allowing allergens to enter the skin and interact with components of the immune system [R].

IL13 and ARDS

Acute respiratory distress syndrome (ARDS) is a sudden lung failure caused by blood poisoning (sepsis), severe pneumonia, or other critical conditions. Uncontrolled inflammation caused by excessive cytokine release is the hallmark of ARDS. The stimulation of white blood cells can cause a so-called cytokine storm and do more damage than the infection itself  [R, R, R, R, R, R, R, R].

The battle between pro- and anti-inflammatory cytokines can determine ARDS occurrence and severity. The anti-inflammatory effects of IL-13 may prevent lung injury in critically ill patients [R].

According to preliminary research, some ARDS patients may have lower IL-13 levels and thus lack the protective effects. However, there’s conflicting evidence about the role of this cytokine in ARDS, calling for further investigation [R, R].

A Russian study of 430 patients found a link between one IL13 variant and ARDS. Critically ill patients with the “A” allele at rs20541 had nearly a two times lower likelihood of developing ARDS [R].

However, the same allele has a robust link with allergic tendencies, asthma, and chronic lung disease (COPD), which are Th2-dominant conditions [R, R, R].

This variant is an example of complex genetic factors that can be both positive and negative, depending on the circumstances. In summary, it may play a role in allergic respiratory complications but also protect against acute lung failure.