Noncellular ComponentCytokines (Table 1-8) - Cytokines are small proteins secreted by cells that modulate functional properties of the cytokine producing cell or other local/distant cells (autocrine, paracrine, or endocrine manner); plays crucial role in intercellular communication and affects proliferation and differentation of cells; vast majority of cytokines produced by T cells
- Cytokines classified as interleukins, lymphokines, or chemokines based on their function and cellular source; chemokine is a specific class of cytokines with ability to stimulate leukocyte mobility (chemoattraction) and direct migration (chemotaxis)
- Keratinocytes: major source of cytokines in skin, including TNFα, IL-1, IL-6, IL-7, IL-8, IL-10, and IL-18
| | | | | | | Table 1-8 Cytokines | | Cytokine | | Produced by | | Function | | IL-1 | | Monocytes, macrophages, keratinocyte | | Proinflammatory (Corticosteroid downregulates IL-1 production)
Triggers host innate inflammatory response (i.e., macrophages), induces fever, ↑ production of acute phase reactant, vascular endothelial cells with ↑ expression of adhesion molecules (↑ chemotaxis) | | IL-2 | | Activated T cells | | T cell stimulator
↑ Growth and activation of T, NK, and B cells | | IL-3 | | T cells | | Growth of mast cells and enhanced basophil production, stimulates myeloid cells | | IL-4 | | TH2 cells | | ↑ TH2 response
Stimulates B/T cells (TH2), induces B cell class switching to IgE, ↑ MHC II production | | IL-5 | | TH2 cells, mast cells | | Eosinophil stimulator
Also stimulates B cells and Ig production (↑ IgA production) | | IL-6 | | Mainly lymphoid cells, endothelial cells | | Proinflammatory
Produces acute phase proteins, sitmulates B cells to differentiate to plasma cells and ↑ antibody secretion, ↑ neutrophil production | | IL-8 | | Keratinocyte, endothelial cells | | Neutrophil chemotaxis
Member of CXC chemokine family | | IL-10 | | TH2 cells, keratinocytes | | Anti-inflammatory
Inhibits proinflammatory cytokines along with inhibition of macrophages/dendritic cells; activates B cells, downregulates TH1 response | | IL-12 | | Mononuclear phagocytes,
dendritic cells | | ↑ TH1 response
Proinflammatory cytokine, induces cell-mediated immunity (i.e., NK cells), ↑synthesis of IFNγ and TNFα | | IL-15 | | Mononuclear phagocytes | | Proliferative
↑ NK cell proliferation, ± T cell growth factor | | IL-18 | | Activated T cells | | Proinflammatory
IFNγ-inducing factor | | TNFα | | T cell, mononuclear phagocyte, mast cell, keratinocytes | | Proinflammatory
Releases other proinflammatory cytokines (IL-1, IL-6), ↑ MHC I/II, activates T/B cells, induces fever and catabolism (cachexia) | | IFNα | | Leukocytes, fibroblasts | | Antiproliferative
Antiviral, anti-oncogenic, ↑ MHC I/II expression, activation of NK cells, antifibrotic properties, inhibits angiogenesis | | IFNβ | | | | IFNγ | | T cells, NK cells | | ↑ TH1 response
Primes macrophages, causes B cell switching to produce Ab, good for opsonization, ↑ MHC expression, inhibit TH2 response | | TGF-β | | Activated platelets, keratinocyte | | Anti-inflammatory
Induces apoptosis, inhibits growth of many cell types, counteracts proinflammatory cytokines | | | | | | | | | | | | | | | | | | | | | | | Of note, aberrant TGF-β expression is implicated in the pathogenesis of fibrosis in systemic sclerosis (SSc) | | | | | | | | |
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