Understanding Growth factors and Cytokines

Growth Factors-

Growth factors are proteins or steroid hormones that bind to receptors on cell surface and promote cellular growth, proliferation and differentiation. These can also be defined as the extracellular signalling molecules that are involved in cell-cell communication. Growth factors are known to regulate cellular processes by signalling information between the various cells. Growth factors are thought to have evolved in order to perform cell-cell communication in multicellular organisms. This cell-cell communication occurs by cell signalling which is a system of communication by which cells detect and respond to any external stimuli present. Cells respond to chemical signals which are primarily synthesized and released by adjacent cells but, signals can be anything from light, temperature, touch, pH etc. The cells response according to the stimuli and the response were initially thought to be growth and proliferation hence, the term growth factor was used but, studies have shown that growth factors are not only important for growth and proliferation but, also for cell differentiation, survival, division, synthesis, transformation, cell death and motility depending upon the stimuli. Most of the growth factors act on neighbouring target cells by binding to specific high affinity plasma membrane receptors [Thomas et al 2008]. This binding to specific receptors causes growth factors to induce signal transduction pathways which leads to the activation of effector mechanisms present within the cell that responds. Nerve growth factor (NGF) was the first growth factor being isolated and studied [Cohen & Levi-Montalcini 1957] soon followed by epidermal growth factor [Cohen 1965].Growth factors are named majorly on the basis of the cell type or the tissue from which the factor was first isolated e.g. Platelet derived growth factor (PDGF) and Brain derived growth factor (BDGF) or on the basis of the response that is elicited in the targeted cell upon receptor binding e.g. Hepatocyte growth factor (HGF) and Fibroblast growth factor (FGF) or on the basis of the main action that is stimulated e.g. Transforming growth factor (TGF) and Bone morphogenetic factor (BMP).[Thomas et al 2008]

Cytokines-

Initially, cytokines were defined as the extracellular signalling proteins that were responsible for interaction with the immune cells while growth factors were thought to act on other cells. Hence they were collectively grouped as immunocytokines or immunokines. But, now evidence shows that these signalling proteins mediate and regulate inflammation, haematopoiesis and other cellular processes as well apart from immunity and hence, are termed as cytokines [Thomas et al 2008]. Cytokines are produced by cells other than immune cells also. They are also produced by glial cells of the nervous system. Different types of cells respond in different manner to variety of cytokines. Sometimes, the terms growth factors and cytokines are used interchangeably as clear demarcation is not possible due to diversity of their functions. Interleukins (IL), Growth hormone, Tumour necrosis factor (TNF) and interferons (INF) comprise main cytokines. Cytokines belong to a unique family of growth factors which are secreted mainly from leukocytes. Those secreted from lymphocytes are termed as lymphokines while the ones secreted by monocytes or macrophages are known as monokines. Many lymphokines are called as interleukins as they are not secreted by leukocytes but, affect cellular responses of leukocytes and chemokines are cytokines having chemotactic activities. Cytokines are known to activate phagocytic cells and stimulate humoral as well as cellular immunity. Apart from regulating immunity, haematopoiesis and inflammation, cytokines are now known to be involved in neurogenesis, oncogenesis and embryonic development of an organism. Moreover, cytokines influence the actions of other cytokines and act in cascades [Naruse K et al 2010].

The mechanism of action of cytokines is by paracrine signalling i.e. a target cell is in the vicinity of emitting cell, autocrine signalling i.e. when a signal targets the cell itself and juxtacrine signalling in which signals target adjacent cells through a synapse [Thomas et al 2008]. It is known that traditional cytokines like IL-1 and IL-6 are secreted by non-immune cells whereas, growth factors like FGF and TGFβ-2 are secreted by cells of immune system. IL-1 is an inflammatory cytokine which is produced by activated macrophages and it is known to promote activation and secretion of cytokines and other acute-phase proteins. IL-2 is primarily produced by T helper cells. It is the major growth factor for T cells and it promotes the growth of B cells and can activate NK cells and monocytes. IL-4 is produced by T cells and mast cells.IL-5 is a cytokine produced by Th2 cells and it promotes the growth and differentiation of B cells and eosinophiles. IL-7 is responsible for apoptosis of tumour cells and causes differentiation of cells from a subgroup of acute myeloblastic leukaemia. IL-8 acts as a chemotactic factor that attracts neutrophils, basophils and T-Cells to sites of inflammation. IL- 10 is mainly an inhibitory cytokine which is produced by activated macrophages, B cells, and T helper cells. TNF-α is an important mediator of acute inflammation and is produced by activated macrophages in response to microbes, for example reaction to the presence of the lipopolysaccharide (LPS) of Gram negative bacteria. Interferon-γ (IFN-γ) is an important cytokine produced by Th1 (T helper type 1) cells and NK cells. IFN-γ has numerous functions in both innate immune and adaptive immune systems. 

Chemokines are chemotactic cytokines produced by many kinds of leukocytes and other cell types. Chemokines recruit leukocytes to sites of infection and play a role in lymphocyte trafficking. Transforming growth factor-β (TGF-β) is a cytokine produced by T cell, macrophages, and many other cell types. It is an inhibitory cytokine that inhibits the proliferation of T cells and blocks the effects of pro-inflammatory cytokines.TNF-α, IL-1, IL-10, IL-12, IFN-α, IFN-β, IFN-γ, and chemokines play an important role in the innate immune system. Though the terms growth factors and cytokines are used interchangeably but, the term growth factor is used with respect to proliferation of cells whereas, cytokine is a neutral term which means it can cause cells to proliferate, differentiate, and divide or any other effect. [Kayisli et al2009][Elgert 1996][Naruse K et al 2010]

                                                               Dr.Bharati Sood