Cytokines Basic introduction

Contents Definition General characteristics Types of cytokines Cytokine receptors and their types Biological functions of cytokines Therapeutic uses of cytokines Cytokines in hematopoiesis

Cytokines The complex interactions among lymphoid cells, inflammatory cells and hematopoietic cells are mediated by a group of proteins collectively designated as cytokines to define their role in cell-to-cell communication. These are low molecular weight regulatory proteins or glycoproteins secreted by white blood cells or various other cells in the body in response to number of stimuli. These proteins assist in regulating the development of immune effector cells, and some cytokines possess direct effect or functions.

General Characteristics Cytokines bind to specific receptors on the membranes of target cells, triggers the signal transduction which alters the gene expression of the target cells.

Cytokine exerts three type of actions Autocrine - It binds to receptors on the membrane of same cell that secreted it. Paracrine – It binds to receptor on a target cell in close proximity to the producer cell. Endocrine - It binds to receptor on target cell in distant parts of body through circulatory system.

Cytokines also exhibits Pleiotropy - Cytokine that has different biological effects on different target cells. Redundancy- Two or more cytokines that mediate similar functions.

Synergism- When the combined effect of two cytokines on cellular activity is greater than the additive effect of individual cytokines. Antagonism - When effects of one cytokine inhibit or offset the effects of another cytokine.

Cascade induction - When the action of one cytokine on a target cell induces that cell to produce one or more other cytokines.

They shows their biological effects at picomolar concentrations. They mediate and regulate the immune system. Their secretion is brief and self-limited. Action of cytokine may be local or systemic. They act as intracellular messengers. They generally have a molecular mass less than 30 kDa.

Types Of Cytokines Lymphokines - Cytokines secreted by lymphocytes. Monokines - Cytokines secreted by monocytes and macrophages. Interleukins - Cytokines secreted by some leukocytes and acts upon other leukocytes. Interferons - Cytokines secreted in response to viral infections or other stimuli. Tumor necrosis factors – These are secreted by some Macrophages and they induces the necrosis of tumor cells and pro inflammatory actions Chemokines - Low molecular wt. cytokines that affect chemotaxis and other aspects of leukocytes behaviour.

Structural Families of Cytokines Hematopoietin Family -  -helical structure prevalence. Little or no  -sheet. Examples are IL-2 and IL-4. Amino acid sequences vary considerably. Interferon Family Tumor Necrosis Family Chemokine Family

Structure of Interleukin-2 Primary structure of IL-2 showing  -helical regions (  and A–D) and connecting chains of the molecule. Proposed three-dimensional model of IL-2. Here the  -helices are shown in red and the  -sheets in blue.

Structure of Interleukin-4 Ribbon model of IL-4 deduced from x-ray crystallographic analysis of the molecule. Here the  -helices are shown in red and the  -sheets in blue. The structures of other cytokines belonging to the Hematopoietin family are thought to be generally similar.