Posted: 11th October 2026 | Posted by: AdminMR
UKallergy · Immunology explained
Type 2 inflammation and the nervous system
Why allergic disease itches, blocks and irritates:
exploring the connections between eczema, asthma,
nasal polyps and eosinophilic oesophagitis.
Asthma
Nasal polyps
Eosinophilic oesophagitis
What is type 2 inflammation?
Type 2 inflammation is an immune response that helps defend
against parasites and supports tissue repair. In disease,
persistent activation can disrupt the protective barriers of
the skin and airways. T helper 2 (Th2) cells, group 2 innate
lymphoid cells (ILC2s), eosinophils and other immune cells participate.
1, 2
Cytokines are signalling proteins that cells
use to communicate. IL-4, IL-5 and IL-13 are central to type 2
responses; IL-31 is particularly relevant to itch. Barrier
tissues also release warning signals, including IL-25, IL-33
and thymic stromal lymphopoietin (TSLP).
1
Type 2 inflammation is not the same as a positive allergy test.
IgE-mediated allergy and type 2 inflammatory disease overlap,
but they are not interchangeable. The pathway alone does not
identify an external allergen causing a person’s symptoms.
2, 4
On a small screen, swipe the table sideways to view both columns.
| Signal | Main relevance |
|---|---|
| IL-4 |
Promotes Th2 responses and IgE production; also contributes to the sensitisation of itch-related nerves. 1, 3 |
| IL-13 |
Contributes to barrier dysfunction and tissue changes, and can act on sensory neurons. 1, 3 |
| IL-5 |
Supports eosinophil development, survival and activation. Experimental work also links it to airway nerve–immune communication. 1, 2 |
| IL-31 |
A major itch-associated cytokine that signals through receptors on sensory nerves. 1, 5 |
How immune cells and nerves communicate
Sensory nerves detect irritation and carry information to the
nervous system. In inflamed tissues, immune mediators can make
these nerves more responsive. Activated nerves can release
neuropeptides, which influence nearby immune
cells. This two-way relationship is called
neuroimmune cross-talk.
2
The immune–nerve conversation
Including Th2 cells, ILC2s, mast cells and eosinophils
Including IL-4, IL-13 and IL-31
Immune cells influence nerves
Neuropeptide signals
Including substance P and CGRP
Detect irritation and contribute to sensations such as itch
nerves; neuropeptides signal back. These effects depend on the
tissue and context and do not always increase inflammation.
2, 6
Why itch can persist
Oetjen and colleagues demonstrated responses to IL-4 and IL-13
in mouse and human sensory neurons. In mice, neuronal IL-4
receptor alpha and JAK1 signalling were important for chronic
itch. The findings help explain why eczema itch involves more
than histamine alone.
3
Scratching can injure the skin barrier and provoke further
signalling, contributing to an itch–scratch cycle. Immune cells,
skin cells and sensory nerves all participate.
5
The loop is not always harmful.
A 2025 review highlights differences between skin and lung
circuits. For example, CGRP can restrain ILC2 activity in
experimental airway models. Findings from animals do not
automatically establish the same effects in patients.
6
One immune pattern, different organs
Shared type 2 biology helps explain why some people have more
than one of these conditions. However, their symptoms and
mechanisms differ, and not every case of asthma or nasal
disease has a type 2 pattern.
4
Skin
Eczema and chronic itch
Atopic dermatitis involves barrier disruption and inflammation.
Nerve sensitisation contributes to itch, alongside the visible
skin changes.
3, 5
Upper airways
Nasal polyps and smell loss
Chronic rhinosinusitis with nasal polyps can affect smell.
Obstruction and inflammation are important; research also
examines effects on the olfactory system.
4
These symptoms have other possible causes. Having itch, cough or
swallowing problems does not by itself establish type 2 inflammation.
Why this research matters for treatment
Understanding the pathways has supported treatments directed at
cytokines, their receptors or intracellular signalling. Examples
include approaches targeting IL-4/IL-13, IL-5, IL-31 and JAK
pathways. Different medicines have different indications, risks
and monitoring requirements; they cannot be used interchangeably
across all these conditions.
1, 4
An example of clinical translation is the MHRA’s February 2025
approval of nemolizumab, an IL-31 receptor blocker, for specified
patients with moderate-to-severe atopic dermatitis or prurigo
nodularis. The approval included additional eligibility and
treatment conditions; it is not a treatment recommendation for
every person with itch.
8
Treatment decisions require assessment of the diagnosis,
severity, associated conditions and response to standard care.
Current licensing and NHS access should be checked for the
individual medicine and indication.
When to seek medical advice
Discuss persistent itch, eczema affecting sleep, ongoing smell
loss, wheeze or cough with your GP. Difficulty swallowing or a
sensation of food sticking warrants urgent GP advice or NHS 111.
9
Food lodged in the oesophagus requires urgent assessment in A&E.
This is especially important if you cannot swallow saliva.
7
Call 999 for severe breathing difficulty or choking.
Common questions
Is type 2 inflammation the same as type 2 diabetes?
No. Here, “type 2” describes an immune response;
it does not refer to diabetes.
Can an allergy blood test diagnose these conditions?
An IgE test assesses sensitisation to particular allergens.
It does not, on its own, diagnose eczema, asthma, nasal polyps
or EoE. Assessment depends on the symptoms and condition;
EoE usually requires endoscopy and oesophageal biopsies.
7
Why might an antihistamine not stop eczema itch?
Eczema itch involves pathways beyond histamine, including
cytokine signalling and nerve sensitisation. This helps
explain why antihistamines may have limited effects on the
underlying itch.
3, 5
Does one medicine treat every type 2 condition?
No. Sharing a biological pathway does not make conditions
identical. A medicine’s evidence, licence and suitability
need to be considered for each diagnosis.
Related reading from UKallergy
References and further reading
A selected reading list of research, clinical guidance and
regulatory information. Reviews summarise evidence from both
human and experimental studies.
-
Haddad E-B, Cyr SL, Arima K, et al.
Current and emerging strategies to inhibit type 2 inflammation
in atopic dermatitis.
Dermatol Ther (Heidelb). 2022;12:1501–1533.
Read the review
. -
Kabata H, Artis D.
Neuro-immune crosstalk and allergic inflammation.
J Clin Invest. 2019;129(4):1475–1482.
Read the review
. -
Oetjen LK, Mack MR, Feng J, et al.
Sensory neurons co-opt classical immune signaling pathways
to mediate chronic itch.
Cell. 2017;171(1):217–228.e13.
Read the study
. -
Kim B, Rothenberg ME, Sun X, et al.
Neuroimmune interplay during type 2 inflammation:
symptoms, mechanisms, and therapeutic targets in atopic diseases.
J Allergy Clin Immunol. 2024;153(4):879–893.
Read the review
. -
Wang F, Kim BS.
Itch: a paradigm of neuroimmune crosstalk.
Immunity. 2020;52(5):753–766.
Read the review
. -
Tamari M, Ver Heul AM.
Neuroimmune mechanisms of type 2 inflammation in the skin and lung.
Allergol Int. 2025;74(2):177–186.
Read the review
. -
BSG/BSPGHAN joint consensus guidelines on the diagnosis and
management of eosinophilic oesophagitis in children and adults.
Gut. 2022.
Read the guidelines
. -
MHRA. Nemolizumab approved to treat prurigo nodularis and
atopic dermatitis (eczema) for patients in the UK.
17 February 2025.
Read the approval announcement
. -
NHS. Dysphagia (swallowing problems).
Read the patient guidance
.