Table 2: Summary of the main features of pro- and anti-inflammatory cytokines.

CytokineMain sourcesMain functionsInteractions with other cytokinesAlteration/involvement in diseasesPhysiologic inhibitors and therapeutic targeting strategiesReferences

Proinflammatory

 TNF- Immune cells of the innate and adaptive immune system (mainly macrophages and lymphocytes); fibroblastsDifferentiation and activation of immune cells; induction of fever and coagulation; cachexia; apoptosisPromote the release of downstream proinflammatory effector moleculesRole in atherosclerosis, RA, Alzheimer’s disease, autoimmune diseases, and cancersTNFRs; anti-TNF Ab; TNFR inhibitors[3543]

 IL-1Induction of fever and coagulation; hematopoiesis; promotes the extravasation of inflammatory cellsRole in autoinflammatory diseases, heart failure, and diabetesIL-1R2; IL-1Ra; anti-IL-1 mAb[16, 38, 39, 4448]

 IL-6Activation of B and T lymphocytes; modulation of hematopoiesis and acute phase response; induction of feverReleased in response to TNF- and IL-1 but inhibits their release; promotes anti-inflammatory responses (sTNFRs, IL-1Ra, and TGF- ) Serum levels following burns, major surgery, in sepsis, RA, and Crohn’s diseasesIL-6R, anti-IL-6 Ab, and anti-IL-6R Ab[4963]

 IL-12Monocytes/macrophages; Neutrophils; dendritic cellsPromotes type 1 adaptive immune response and differentiation of TH1 T lymphocytes; induces antitumor immune responseInduces IFN- productionRole in cancerAnti-IL-12 mAb[6467]

 IFN- NK cells; TH1 and CD8+ cytotoxic T-cellsAntiviral activity; potentially reverses immunoparalysis in sepsisReleased in response to TNF-α, IL-12, and IL-18 Serum levels in sepsisrIFN- [6873]

 MIFPituitary cells; monocytes/macrophagesActivation of macrophages and T-cells; overrides the anti-inflammatory effect of glucocorticoidsReleased in response to infection, inflammation, and proinflammatory cytokines; promotes the release of proinflammatory effector molecules Serum levels in acute and chronic inflammatory diseases; role in cancerSmall molecule inhibitors (ISO-1, benzoxazol-2-ones); human anti-MIF Ab; MIF-derived peptide sequences[69, 7484]

Anti-inflammatory

 IL-10Immune cells of the innate and adaptive immune systemImmunosuppressive properties, such as the impairment of antigen presentation and phagocytosisSuppress the release of proinflammatory cytokines; stimulate production of sTNFRs and IL-1RaDysregulated in autoimmune diseasesrIL-10[8588]

 TGF- Macrophages; smooth muscle cellsInvolved in tissue repair, fibrosis, and sepsis-induced immunosuppression Serum levels in sepsis; upregulated in cancer and fibrosisSmall molecule inhibitors; anti-TGF- mAb[8994]

 IL-4TH2 T lymphocytes; mast cells; basophils; eosinophilsPromotes differentiation of TH2 T lymphocytesInduces release of IL-4 and IL-13 from macrophagesRole in scleroderma, asthma, and tuberculosisAnti-IL-4R mAb[95, 96]

RA: rheumatoid arthritis; sTNFRs: soluble TNF receptors; mAb: monoclonal antibody; IL-1Ra: IL-1 receptor antagonist; rIFN- : recombinant IFN- ; ISO-1: (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester.