INTERLEUKINS IN THERAPEUTICS

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ABOUT AUTHOR:
Anjan Khadka
Department of Pharmacology,
AFMC, Pune, India
anjankhadka14@yahoo.com

ABSTRACT:
Interleukins are a subset of a larger group of cellular messenger molecules called cytokines, which are modulators of cellular behaviour. On the basis of their respective cytokine profiles, responses to chemokines, and interactions with other cells, these T-cell subsets can promote different types of inflammatory responses. During the development of allergic disease, effector TH2 cells produce IL-4, IL-5, IL-9, and IL-32.  IL-25, IL- 31, and IL-33 contributes to TH2 responses and inflammation. These cytokines have roles in production of allergen-specific IgE, eosinophilia, and mucus. ILs have role in therapeutics as well as diagnosis and prognosis as biomarker in various conditions. Therapeutic targeting of the IL considered to be rational treatment strategy and promising biologic therapy.

REFERENCE ID: PHARMATUTOR-ART-2139

PharmaTutor (ISSN: 2347 - 7881)

Volume 2, Issue 4

Received On: 13/02/2014; Accepted On: 21/02/2014; Published On: 01/04/2014

How to cite this article: A Khadka, Interleukins in Therapeutics, PharmaTutor, 2014, 2(4), 67-72

INTRODUCTION:
Interleukins are group of cytokines that were first seen to be expressed by leucocytes and they interact between cells of the immune systems. It is termed by Dr. Vern Paetkau (University of Victoria) in 1979. Interleukins (IL) are able to promote cell growth, differentiation, and functional activation. The question of how diverse cell types communicate with each other hadled to the discovery of interleukins. The name interleukin was chosen because it reflected the basic property of these mediators to serve as communication links between leukocytes.1,2 Effects of ILs has greatly increased since the discoveries of monocyte IL (called IL-1) and lymphocyte IL (called IL-2); more than 40 cytokines are now designated as ILs.3

Cytokines are low molecular weight regulatory proteins or glycoproteins secreted by white blood cells & other cells in the body in response to various stimuli.Cytokine is a word that comes from cyto meaning “cell” and kinin meaning ‘hormones’. It was Stanley Cohen in 1974 who for the first time introduced the term ‘‘cytokine’’. It includes lymphokines, monokines, interleukins, and colony stimulating factors (CSFs), interferons (IFNs), tumor necrosis factor (TNF) and chemokines. The majority of interleukins are synthesized by helper CD4 T lymphocytes, as well as through monocytes, macrophages, and endothelial cells. They promote the development and differentiation of T, B, and hematopoietic cells.1,2,3

Properties of cytokines: Based on function1,3

  1. Hormone like action: autocrine, paracrine, endocrine
  2. One cytokine can affect more than one types of cells – Pleiotropism
  3. Different cytokines can perform some similar functions - Redundancy
  4. One cytokine can influence the function(s) and/or production of other cytokines- Multifunctional

Classification of Cytokines:Based on principal action2,3

Principal action

Mediators of innate immunity

Mediators of specific immunity

Stimulate growth of BM progenitors

Source

Mononuclear phagocytes

Ag stimulated T lymphocytes

BM cells, T cells

Cytokines

IL1

IL6

IL10

IL12

IL15

Type I IFN

Chemokines

IL2

IL4

IL5

TGF ß

IFN α

TNF

IL3

IL7

GM-CSF

M-CSF

G-CSF

Classification of interleukins: Based on shared structural characteristics, and/or shared receptor subunits and/or shared chromosomal locations2,3,4,5

Family

Interleukins

Functions

IL-1 family

IL-1α, IL-1β, IL-18 , IL-33

Co-stimulation of T helper cells; Maturationand proliferation of B cells; Activation of NK cells; Role in inflammation acute phase reactions and fever.

IL-2 family

IL-2, IL-4,  IL-7, IL-9,  IL-13, IL-15, IL-21

Stimulates growth and differentiation of  cell response; IgG and IgE synthesis (important in allergic response);

Used as Immunotherapy to treat cancer or suppressed for transplant patients; Used in clinical trials to raise CD4 counts in HIV positive patients

IL-10 family

IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, IL-29

Cytokine production; Histamine release; Inhibits Th1 cytokine production (IFN gamma, TNF-beta, IL-2); Osteoclast formation

IL-12 family

IL-12, IL-23, IL-27

Differentiation into cytotoxic T cells with IL-2; Increase IFN-gamma and TNF-alpha, Decrease IL-10; iincrease TNF-alpha and  IFN-gamma

IL-17 family

IL-17A–F, IL-25

Angiogenesis; Increase inflammatory cytokines; Pro inflammatory role in asthma;  Induces production of IL-4, IL-5 and IL-13, which stimulate eosinophil expansion

Family of ‘Like’ cytokines

IL-3, IL-5 ,IL-6 and IL-11

Differentiation of activated B cells into plasma cell; Antibody secretion; Osteoclast formation; Acute phase reaction, hematopoiesis, differentiation, inflammation, etc.

Fig: Interleukin-6 as multifunctional interleukins3,8

Fig: Cytokine cascade links inflammatory and immune responses3,8,9

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