Table 3.

General functions of cytokines measured in the present study

Item	Class	Function	Citation
IFN-αA	Anti-inflammatory Pro-inflammatory	- Inhibits multiplication of viruses - Stimulation of innate and adaptive immune cells and antibody class switching - Immunosuppressive with prolonged activity	Cha et al. (2014) Tilg and Peschel (1996)
IFN-γ	Pro-inflammatory	- Upregulates activity of CD4 helper T cells, CD8 cytotoxic T cells, NK cells, dendrites, and macrophages - Potentiates pro-inflammatory signaling and antigen presentation - Antagonizes IL-10 and TGF-β	Castro et al. (2018) Kopitar-Jerala (2017)
IL-13	Anti-inflammatory	- Inhibits pro-inflammatory cytokine production from macrophages - Central mediator of IgE	Dembic (2015) de Vries (1998)
IL-1α	Pro-inflammatory	- Simulates activity of genes related to inflammation and immune processes - Cell recruitment by promoting expression of adhesion molecules and chemokine production	Gabay et al. (2010) Medline (2022)
IL-1F5	Pro-inflammatory	- Also known as IL-36RN - Proposed to play a role in skin inflammation - Might be involved in innate immune response to fungal pathogens	Blumberg et al. (2007)
IL-21	Anti-inflammatory Pro-inflammatory	- Increases production of IL-17 by promoting differentiation of naïve Th cells to Th17 cells, upregulates IL-6 - Produced by activated CD4+ T cells; initiates and sustains antibody production and mediates antibody class switching - Promotes migration of neutrophils and NK cells to cite of inflammation, terminal conversion of B cells to plasma cells - In the presence of bacterial LPS: inhibits B cell proliferation and dendrite activation - Balances inflammatory response by increasing IL-10 production and decreasing TNF-α production	Davis et al. (2007) Mootha et al. (2021)
IP-10	Chemokine	- Chemotactic agent for T cells, NK cells, monocytes, macrophages, and dendrites - Produced by many cell types in response to IFN-γ and LPS	Chen et al. (2020) Dufour et al. (2002)
MIG	Chemokine Pro-inflammatory	- “Monokine induced by gamma”, or CXCL9 - Recruitment of activated T cells to sites of infection - Induced by IFN-γ, might amplify the IFN-γ signal - May be a functional measure of bioactive IFN-γ activity that is more sensitive than direct measurement of IFN-γ	Berthoud et al. (2009)
MIP-1β	Pro-inflammatory	- Attracts several types of immune cells to the site of microbial infections - Stimulates production of pro-inflammatory cytokines, mast cell degranulation, and NK cell activation	Menten et al. (2002)
TNF-α	Pro-inflammatory	- Among the most important pro-inflammatory cytokines in mounting a proper, robust immune response - Participates in vasodilatation, expression of adhesion molecules and leukocyte recruitment, regulates blood coagulation, contributes to oxidative stress, indirectly induces fever - Activation of neutrophils and platelets and enhances killing abilities of NK cells and macrophages. Upregulates subsequent cytokine production - Bacterial LPS is one of the main stimulants of TNF-α production	Idriss and Naismith (2000) Zelová and Hošek (2013)
aFGF bFGF	Growth factor	- Fibroblast growth factors. Prototypic members have different isoelectric points: - aFGF = acidic. Greatest expression in brain, retina, bone matrix, osteosarcomas - bFGF = basic. Greatest expression in pituitary gland, neural tissue, adrenal cortex, corpus luteum, placenta - Regulation of cell proliferation and differentiation, critical for normal fetal development, tissue maintenance, and somatic stem cell development - During inflammation: members of the FGF family facilitate the repair process	DePhillips and Lenhoff (2004) Marega et al. (2021) Yun et al. (2010)
GASP-1	Myokine	- Negative regulation of muscle mass - Regulates activation of myostatin via proteolytic cleavage	Elkina et al. (2011) Périè et al. (2017)
IGF-1	Growth factor Anti-inflammatory Pro-inflammatory	- Hormone that is a major mediator of somatic growth and anabolic responses in several cells and tissues - During inflammation: can modulate immunity in various immune cells, primarily lymphocytes and monocytes, with pro- and anti-inflammatory effects depending on the magnitude of the stimulus and the type of immune cell - Mechanisms of growth hormone and IGF-1 effects on the inflammatory response are not completely understood	Johnson et al. (1996) Wolters et al. (2017)
IL-2	Pro-inflammatory	- Produced by activated T lymphocytes and upregulates the growth and activity of T lymphocytes, B lymphocytes, NK cells, and development of the immune system - Strong activator of TNF-α, IFN-γ, and IL-1 production - Depending on the quantity of interaction with the IL-2 receptor, can be immunosuppressive via production of effector immune cells and regulatory T cells	Hodi and Soiffer (2002) Mitoma et al. (2021)
IL-4	Immunoregulator	- “Prototypic immunoregulatory cytokine”: regulation of antibody production, hematopoiesis, inflammation, effector T-cell responses. Mainly produced by activated T cells - Augments expression of major histability complexes, promotes secretion of IgE and IgG - Inhibits production of inflammatory cytokines, primarily TNF-α, IL-6, and IL-1 - Pathways to determine the fate of Th lymphocytes, and promoting Th2 differentiation while inhibiting Th1 differentiation	Brown and Hural (1997) Curtis (2006) Luzina et al. (2012) Smiley and Grusby (1998)
IL-15	Pro-inflammatory	- Important during the innate inflammatory response to microbial and parasitic pathogens, and mounting a protective immune response - Critical to the development, differentiation, and survival of NK cells - In mice: expressed by monocytes and macrophages primed with microbial PAMPs or IFN-γ - Is not downregulated by inhibitory cytokines, such as IL-4 or IL-13 - Closely related to IL-2	Marks-Konczalik et al. (2000) Perera et al. (2012)
MCP-1	Chemokine	- “Monocyte chemoattractant protein” - Regulates the migration and translocation of monocytes and macrophages	Deshmane et al. (2009)
NCAM-1	Adhesion molecule	- “Neural cell adhesion molecule” - Part of the immunoglobulin superfamily that is expressed in neurons and glial cells - Important for the development of the central nervous system and synaptic plasticity - Mode of action includes regulation of cell adhesion, migration, and neurite growth	Hübschmann et al. (2005) Jesudas et al. (2020)
VEGF	Pro-inflammatory	- “Vascular endothelial growth factor” - Enhances endothelial permeability by upregulating the expression of adhesion molecules on endothelial cells, acts as chemoattractant for monocytes - During inflammation: produced by T cells, synovial cells, smooth muscle cells, and epithelial cells at the site of inflammation that promotes angiogenesis and exacerbates the severity of the reaction	Angelo and Kurzrock (2007) Reinders et al. (2003)
ANG-1	Anti-inflammatory Pro-inflammatory	- “Angiogenic growth factor” - Upregulates the growth, maturation, and structural integrity of blood vessels - Involved in cellular signaling that activates production of pro-inflammatory cytokines and macrophage differentiation - Assists in endothelial integrity, which can temper the inflammatory response by preventing vascular leakage - Involved in neutrophil recruitment via production of IL-8, a neutrophil chemotactic factor	Pizurki et al. (2003) Seok et al. (2013)
CD40	Ligand	- Expressed almost exclusively by CD4+ cells - Belongs to the tumor necrosis factor superfamily - Mediates a variety of activities, including the activation of B cells and subsequent isotype switching, immunoglobulin production, and memory, and monocyte activation - Without CD40, system cannot execute immunoglobulin class switching, and only IgM class antibodies can be produced	Alegre et al. (1998) Chan and Rainer (2013) Manzoor (2015)
Decorin	Pro-inflammatory	- Involved in extensive signaling network to regulate cytokine and growth factor production - Upregulates synthesis of TNF-α and IL-12 following binding to TLR2 and TLR4 on the surface of macrophages	Dong et al. (2022)
IFN-β	Anti-inflammatory Pro-inflammatory	- Regulates cytokine and chemokine production, which in turn regulate inflammation - Regulates the development of nearly all effector cells of both innate and adaptive immunity - Modulates expression of TNF-α and IL-10 in peripheral mononuclear cells, decreases TNF-α expression in monocytes, and increases expression of IL-10 in dendrites	Bolívar et al. (2018)
IL-1β	Pro-inflammatory	- “Master regulator” of inflammation via regulation of innate immunity processes - Expression of IL-1β considered a “priming step”: activated cell must encounter further PAMP or DAMP - Leukocytic pyrogen, mediates fever, and induces several components of the APR - Critical in mounting a robust inflammatory response, but chronic exposure exacerbates tissue damage - Stimulus is not well-defined; purportedly continuously secreted, with serum concentration reflective of the strength of the stimulus and the extracellular requirement	Lopez-Castejon and Brough (2011) Kaneko et al. (2019)
IL-10	Anti-inflammatory	- Potent anti-inflammatory agent - Inhibits synthesis of pro-inflammatory cytokines, and downregulates antigen presentation to monocytes, macrophages, and dendrites - Limits T cell activation and proliferation - Monocytes and macrophages are the primary targets	Islam et al. (2021) Iyer and Cheng (2012)
IL-17A	Pro-inflammatory	- Potentiates the inflammatory response by inducing granulopoiesis factors and neutrophil-specific chemokines - Production of several mediators of the APR, such as IL-6, and pro-inflammatory cytokines TNF-α and IL-1β - Insufficient to produce a robust immune response on its own, synergistic with other pro-inflammatory mediators to yield sustained neutrophil recruitment to the site of inflammation	Zenobia and Hajishengallis (2015)
IL-18	Pro-inflammatory	- Important in local and systemic inflammation - Promotes the expression of TNF-α and IFN-γ - Regulates activity of Th1 cells, cytotoxic T cells, B cells, NK cells, and macrophages - Stimulates IL-8 production as a neutrophil chemoattractant	Biet et al. (2002)
LIF	Anti-inflammatory Pro-inflammatory	- “Leukemia inhibitory factor” - In humans: A protective cytokine produced early in the inflammatory response that downregulates expression of pro-inflammatory cytokines and growth factors - Promotes the production of APP and is a monocyte chemoattractant	Banner et al. (1998) Yue et al. (2015)
RANTES	Chemokine	- “Regulated on activation normal T cell expressed and secreted” - Chemoattractant for monocytes, NK cells, and eosinophils - Homing and migration factor of effector and memory T cells during the inflammatory response	Crawford et al. (2011)