Contributions of important cytokines, chemokines, colony-stimulating factors, and growth factors to immunologic responses

Immunomodulatory factor	Source	Critical functions	US FDA-approved uses for clinical disease	Targeted agents	Diseases treated
Cytokines
IL-1	Macrophages Many cells	Fever, induces other cytokines, T cell stimulation Induces metalloproteinases and prostaglandins Increases adhesion molecule expression	None reported	Anti-IL-1 beta: Canakinumab (SC) Rilonacept (SC) IL-1 receptor antagonists: Anakinra (SC) OSP-101 (inhaled)	Cryopyrin-associated periodic syndromes (CAPS) Familial cold autoinflammatory syndrome (FCAS) Muckle-Wells syndrome (MWS) Neonatal-onset multisystem inflammatory disorder (NOMID) Deficiency of IL-1 receptor antagonist (DIRA) Tumor necrosis factor receptor 1-associated periodic syndrome (TRAPS) Hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD) Familial Mediterranean fever (FMF) Systemic juvenile idiopathic arthritis (sJIA) Rheumatoid arthritis Bronchiolitis obliterans
IL-2	T cells	Increase T cell proliferation, activates B cells	Aldesleukin (IV): Malignant melanoma Renal cancer	Anti-IL-2 receptor alpha subunit: Basiliximab (IV)	Renal transplant (prophylaxis from graft rejection)
IL-2	T cells	Increase T cell proliferation, activates B cells	Aldesleukin (IV): Malignant melanoma Renal cancer	Anti-CD25 (high-affinity IL-2 receptor): Daclizumab (SC)	Multiple sclerosis
IL-4	T cells	Signal for immunoglobulin switch, increases IgE Decreases production of proinflammatory cytokines Suppresses delayed-type hypersensitivity (Th1 cells)	None reported	Anti-IL-4R alpha (block IL-4 and IL-13 signaling): Dupilumab (SC)	Eczema Asthma
IL-5	T cells	Increases eosinophil production	None reported	Reslizumab (IV) Mepolizumab (SC) Benralizumab (SC)	Eosinophilic asthma Eosinophilic granulomatosis with polyangiitis
IL-6	Many cells	B and T cell proliferation, acute-phase reactants Induces natural protease inhibitor (TIMP)	None reported	Siltuximab (IV) Anti-IL-6 receptor: Tocilizumab (IV/SC) Sarilumab (SC)	Castleman disease Cytokine release syndrome Giant cell arteritis Polyarticular juvenile idiopathic arthritis (pJIA) Rheumatoid arthritis Systemic juvenile idiopathic arthritis (sJIA)
IL-12	Macrophages	Increase IFN-gamma production and Th1 cell differentiation	None reported	Anti-IL-12/IL-23: Ustekinumab (IV/SC)	Crohn disease Plaque psoriasis Psoriatic arthritis
IL-13	T cells	Similar to IL-4	None reported	Anti-IL-4 receptor alpha (block IL-4 and IL-13 signaling): Dupilumab (SC)	Eczema Asthma
IL-15	T cells Macrophages	Induces TNF-alpha release from synovial macrophages, induces mitogenesis, and inhibits apoptosis	None reported	None reported	None reported
IL-17	T cells Innate lymphoid cells	Activates neutrophils and a variety of stromal cells to regulate host defense and also matrix disruption	None reported	Ixekizumab (SC) Secukinumab (SC) Anti-IL-17 receptor alpha: Brodalumab (SC)	Plaque psoriasis Psoriatic arthritis Ankylosing spondylitis
IL-23	Dendritic cells Macrophages	Promotes T cell differentiation, particularly of the Th17 type	None reported	Tildrakizumab (SC) Guselkumab (SC) Anti-IL-12/IL-23: Ustekinumab (IV/SC)	Crohn disease Plaque psoriasis Psoriatic arthritis
TNF-alpha	T cells Macrophages	Cachexia, induces other cytokines, T cell stimulation Induces metalloproteinases and prostaglandins Increases adhesion molecule expression	None reported	Infliximab (IV) Etanercept (SC) Certolizumab (SC) Golimumab (SC) Adalimumab (SC)	Crohn disease Plaque psoriasis Psoriatic arthritis Rheumatoid arthritis Ulcerative colitis Ankylosing spondylitis Polyarticular juvenile idiopathic arthritis (pJIA) Hidradenitis suppurativa Uveitis
IFN-gamma	T cells	Adhesion molecules, HLA-DR expression, activation of T cells, NK cells, macrophages	IFN-gamma 1b (SC): Chronic granulomatous disease (CGD) Malignant osteopetrosis	None reported	None reported
Colony-stimulating factors
GM-CSF	Macrophages Fibroblasts T cells	Myeloid differentiation, macrophage activation	Sargramostim (IV) Acute myeloid leukemia (AML) Bone marrow transplantation (BMT) Autologous peripheral blood stem cell mobilization and collection Hematopoietic radiation injury syndrome	None reported	None reported
G-CSF	Macrophages	Granulocyte differentiation and activation	Filgrastim (SC), pegfilgrastim (SC), and tbo-filgrastim (SC): Myelosuppressive chemotherapy recipients with non-myeloid cancer Acute myeloid leukemia (AML) Bone marrow transplantation (BMT) Hematopoietic radiation injury syndrome Severe chronic neutropenia (SCN)	None reported	None reported
M-CSF	Macrophages	Myeloid differentiation, macrophage activation	None reported	None reported	None reported
Chemokines
C-X-C family	Many cells	Activate neutrophils, chemotactic to neutrophil (IL-8, ENA-78, etc) and T cells	None reported	Anti-CXCR4 (SC)	Peripheral stem cell mobilization
C-C family	Many cells	Chemotactic for monocytes and T cells (MCP-1, MIP-1, etc)	None reported	None reported	None reported
Growth factors
TGF-beta	Many cells	Fibroblast proliferation, collagen and TIMP synthesis Decrease metalloproteinases, decreases T cell proliferation Angiogenesis, decreased proinflammatory cytokines		Pirfenidone (oral)	Idiopathic pulmonary fibrosis
FGF, VEGF	Many cells	Fibroblast proliferation, angiogenesis		Anti-VEGF: Bevacizumab (IV) Ramucirumab (IV) Anti-VEGF receptor: Ziv-aflibercept (IV) Tyrosine kinase inhibitors to block VEGF: Cabozantinib (oral) Axitinib (oral) Vandetanib (oral) Tyrosine kinase inhibitors to block VEGF and PDGF activity: Ponatinib (oral) Pazopanib (oral) Sunitinib (oral) Sorafenib (oral) Regorafenib (oral) Lenvatinib (oral)	Cervical cancer Glioblastoma Ovarian, fallopian tube, or peritoneal cancer Soft-tissue sarcoma Renal cell carcinoma Medullary thyroid cancer Gastrointestinal stromal tumor Advanced pancreatic neuroendocrine tumor Hepatocellular carcinoma Colorectal cancer (metastatic) Acute lymphoblastic leukemia (ALL) Chronic myeloid leukemia (CML) Gastric cancer (advanced/metastatic) Non-small cell lung cancer (NSCLC)
PDGF	Many cells	Fibroblast proliferation		Anti-PDGF receptor alpha: Olaratumab Tyrosine kinase inhibitors to block PDGF activity: Imatinib (oral) Dasatinib (oral) Nilotinib (oral) Bosutinib (oral) Tyrosine kinase inhibitors to block VEGF and PDGF activity: Ponatinib (oral) Pazopanib (oral) Sunitinib (oral) Sorafenib (oral) Regorafenib (oral) Lenvatinib (oral)	Soft-tissue sarcoma Acute lymphoblastic leukemia (ALL) Aggressive systemic mastocytosis Chronic myeloid leukemia (CML) Myelodysplastic syndrome Hypereosinophilic syndrome Gastrointestinal stromal tumor Dermatofibrosarcoma protuberans

IL: interleukin; FDA: Food and Drug Administration; SC: subcutaneous; OSP-101: Onspira 101; IV: intravenous; IgE: immunoglobulin E; Th1: T helper cell type 1; TIMP: tissue inhibitor of metalloproteinase; IFN: interferon; TNF: tumor necrosis factor; Th17: T helper cell type 17; HLA: human leukocyte antigen; NK: natural killer; GM-CSF: granulocyte-macrophage colony-stimulating factor; G-CSF: granulocyte colony-stimulating factor; M-CSF: macrophage colony-stimulating factor; C-X-C family: chemokines with two N-terminal cysteines (C) separated by one amino acid (X); ENA-78: epithelial cell-derived neutrophil-activating peptide; CXCR4: CXC chemokine receptor 4; C-C family: chemokines with two N-terminal cysteines (C); MCP-1: monocyte chemotactic protein 1; MIP-1: macrophage inflammatory protein 1; TGF: transforming growth factor; FGF: fibroblast growth factor; VEGF: vascular endothelial growth factor; PDGF: platelet-derived growth factor.

Graphic 69910 Version 5.0

خرید پکیج

Contributions of important cytokines, chemokines, colony-stimulating factors, and growth factors to immunologic responses