Porth's Pathophysiology, 9e

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UNIT IV Infection, Inflammation, and Immunity

TABLE 13.2 CYTOKINES OF INNATE AND ADAPTIVE IMMUNITY

CYTOKINES

SOURCE

FUNCTION

Interleukin-1 (IL-1)

Macrophages, endothelial cells, some epithelial cells

Wide variety of biologic effects; activates endothelium in inflammation; induces fever and acute-phase response; stimulates neutrophil production Growth factor for activated T cells; induces synthesis of other cytokines; activates cytotoxic T lymphocytes and NK cells Growth factor for progenitor hematopoietic cells Promotes growth and survival of T, B, and mast cells; causes T 2 H cell differentiation; activates B cells and eosinophils; and induces IgE-type responses Stimulates the liver to produce mediators of acute-phase inflammatory response; also induces proliferation of antibody-producing cells by the adaptive immune system Primary function in adaptive immunity; stimulates pre-B cells and thymocyte development and proliferation Primary function in adaptive immunity; chemoattracts neutrophils and T lymphocytes; regulates lymphocyte homing and neutrophil infiltration Inhibitor of activated macrophages and DCs; decreases inflammation by inhibiting T 1 H cells and release of IL-12 from macrophages Enhances NK cell cytotoxicity in innate immunity; induces T 1 H cell differentiation in adaptive immunity Inhibit viral replication; activate NK cells; and increase expression of MHC-I molecules on virus-infected cells Activates macrophages in both innate immune responses and adaptive cell-mediated immune responses; increases expression of MHC-I and MHC-II and ­antigen processing and presentation Induces inflammation, fever, and acute-phase response; activates neutrophils and endothelial cells; kills cells through apoptosis Large family of structurally similar cytokines that stimu- late leukocyte movement and regulate the migration of leukocytes from the blood to the tissues Promotes neutrophil, eosinophil, and monocyte matura- tion and growth; activates mature granulocytes Promotes growth and maturation of neutrophils ­consumed in inflammatory reactions Promotes growth and maturation of mononuclear phagocytes Induces eosinophil growth and development

Interleukin-2 (IL-2)

CD4 + , CD8 + T cells

Interleukin-3 (IL-3) Interleukin-4 (IL-4)

CD4 + T cells

CD4 + T 2

H cells, mast cells

Interleukin-5 (IL-5) Interleukin-6 (IL-6)

CD4 + T 2

H cells

Macrophages, endothelial cells, T lymphocytes

Interleukin-7 (IL-7)

Bone marrow stromal cells

Interleukin-8 (IL-8)

Macrophages, endothelial cells

Interleukin-10 (IL-10)

Macrophages, some T-helper cells

Interleukin-12 (IL-12)

Macrophages, DCs

Type I interferons (IFN- α , IFN- β )

Macrophages, fibroblasts

Interferon- γ (IFN- γ )

NK cells, CD4 + and CD8 + T lymphocytes

Tumor necrosis factor- α (TNF- α )

Macrophages, T cells

Chemokines

Macrophages, endothelial cells, T lymphocytes

Granulocyte–monocyte CSF (GM-CSF) Granulocyte CSF (G-CSF)

T cells, macrophages, endothelial cells, fibroblasts Macrophages, fibroblasts, endo- thelial cells

Monocyte CSF (M-CSF)

Macrophages, activated T cells, endothelial cells

CSF, colony-stimulating factor; NK, natural killer; T 1

H, T-helper type 1; T 2

H, T-helper type 2; MHC, major

histocompatibility complex.

IFNs are cytokines that primarily protect the host against viral infections and play a role in themodulation of the inflammatory response. IFNs are cell-type specific with IFN- α and IFN- β produced primarily by macrophages and IFN- γ produced pri- marily by T lymphocytes. TNF- α , a cytokine in a class by itself, is one of the most important mediators of the inflam- matory response and is produced by ­macrophages when sur- face toll-like receptors (TLRs) ­recognize ­pathogen-associated

molecular patterns (PAMPs) on the surface of microorgan- isms. 4 TNF- α acts as an endogenous pyogen (fever producer) and induces synthesis of proinflammatory substances in the liver. With prolonged exposure, it has the ability to cause intra- vascular coagulation and subsequent thrombosis production. Despite the diverse functions of the cytokines, they all share certain important properties. All cytokines are secreted in a brief, self-limited manner. They are rarely stored as pre-