Role of eosinophils in Nasal polyposis

Introduction:

Nasal polyposis is a difficult problem to manage because of its high recurrence rate, incomplete understanding of the various pathophysiological factors involved. No specific etiological factor has been attributed to the development of nasal polypi. Hence the current understanding is that it could be caused by multiple different diseases with varying degrees of severity. That is the reason why categorization of unique presentations of nasal polypi will help in better understanding of etiopathogenesis of nasal polypi.

Studies pertaining to different categories of nasal polypi have identified three disease categories of nasal polypi which show prominent tissue eosinophil infiltration. These include:

1. Chronic hyperplastic eosinophilic sinusitis
2. Allergic fungal sinusitis
3. Aspirin induced hypersensitivity

A brief account of development of eosinophils:

Eosinophils develop from the pleuripotent stem cells of bone marrow. These pleuripotent stem cells differentiates into eosinophil / basophil progenitors.

Transcription factors responsible for stimulating the stem cells to produce cells of eosinphil lineage:

1. GATA-1
2. PU.1
3. C/EPB

Among these three transcription factors GATA-1 is the primary transcription factor responsible for eosinophil differentiation of stem cells.

Cytokines responsible for development of eosinophil lineage:

1. IL-3
2. IL-5
3. Granulocyte macrophage colony stimulating factor

Among these cytokines IL-5 is responsible for selective terminal differentiation of eosinophils. It also stimulates the release of eosinophils from the bone marrow into the peripheral circulation. Studies have shown that anti IL-5 drugs when administered have reduced significantly the number of circulating eosinophils. Blocking the tissue effects of these cytokines may significantly lower the number of circulating / tissue eosinophils.

Factors responsible in attracting eosinophils into tissues:

The process of chemotactic migration of eosinophils to the tissues is known as recuritment. This process of recruitment is facilitated by:

1. Cytokines
2. Chemokines
3. Inflammatory mediators

Platelet activation factor is the most potent inflammatory mediator which induces migration of eosinophils (selective) to the tissues. This is usually secreted by mast cells, endothelial cells, macrophages, neutrophils and eosinophils. Eosinophils migrate preferentially to tissues exposed to environment i.e. (nose, gut and lungs). Human tissuee eosinophils is 100 times more in number than eosinophils circulating the the blood.

Many cytokines play a vital role in eosinophil mediated inflammtion by prolonging its life. The classic example of such substance is Tumor Necoris Factor alpha.

Activation of eosinophils causes release of various biological products, the most prominent of them is the granule protein which is cationic and toxic to numerous helminths thus playing a vital role in the body's defence against helminthic infections.

Substances produced by activated eosinophils:

1. Major basic protein
2. Eosinophil cationic protein
3. Eosinophil derived neurotoxin
4. Chemokines

Management of eosinophilic sinusitis:

Accumulation of eosinophils in the nasal mucosa is seen in:

1. Chronic hyperplastic eosinophilic sinusitis
2. Allergic fungal sinusitis
3. Aspirin induced hypersensitivity

These conditions can be pharmacologically manaaged by:

Leukotrienes modifiers – Drugs belonging to this group reduces eosinophil recruitment and activation. Zafirleukast and Monteleukast are classic examples of drugs belonging to this group.

IL-5 blocking – Mepolizumab. This is humanized anti IL-5 drug.