(i) A proinflammatory cytokine. Like TNF-, it mediates generation of acute phase inflammatory and febrile responses and synthesis of APPS, mainly via IL-1. (ii) Increases neutrophil recruitment to MG and enhances their phagocytic and bactericidal activities. (iii) Stimulate secretion of IL-1 itself and IL-6, IL-8, IL-12, and TNF-.
IL-2
CD4+ cells, mainly Th1
(i) Regulates AIS via enhancing the proliferation of B-lymphocytes. (ii) Enhances cytotoxic and bactericidal activities of T-lymphocytes. (iii) Increases plasma cell numbers and activates NK cells.
IL-4
(i) CD4+, mainly Th2 (ii) CD8+/T-suppressors (iii) B-lymphocytes
(i) Contributes to regulation of IIS by regulating the differentiation of T-lymphocytes. It favours development of Th2 subsets. (ii) Exerts a clear inhibitory effect on IFN- production.
(i) A pleiotropic cytokine with both pro- and anti-inflammatory properties. (ii) Shares generation of febrile response and regulates APP synthesis. (iii) Favours the influx of monocytes into the MG. (iv) Induces B-cell differentiation and thus the corresponding Ig production and T-cell activation of neutrophils. (v) Exerts anti-inflammatory action by inhibiting expression of IL-1 and TNF-.
(i) Induces inflammatory response. It is a potent chemoattractant (chemokine) mainly for neutrophil migration into MG with a longer lasting effect and to lesser extent to T-lymphocytes. (ii) Induces neutrophil degranulation. (iii) Enhances microbicidal activities of PMNs and stimulates phagocytosis of opsonised particles.
(i) The main anti-inflammatory cytokine and a principle partner in inflammatory resolution. (ii) Prevents production of proinflammatory cytokines, chemokines, and eicosanoids by leukocytes and downregulates generation of all subtypes of T-helper cells. (iii) Impairs macrophages presentation of Ags to T-cells by downregulating MHC class II expression.
IL-12
(i) Macrophages (ii) B-lymphocytes (iii) Monocytes (iv) Neutrophils
(i) Acts as a mediator between IIS and AIS via regulating differentiation of T-lymphocytes. It favours the polarisation of CD4+ and CD8+ T-cells into Th1 and cytotoxic IFN- producers, respectively. (ii) Acts as a growth factor for activated NK cells and enhances their cytotoxic activities. (iii) By stimulating the production of IFN- by both T-cells and NK cells, it contributes to the activation of macrophages. (iv) Alters Ab responses by enhancing the production of Igs involved in opsonisation and the facilitation of cell-mediated responses, while impairing the production of Igs involved in mediating Th2 humoral IRs. (v) Like IFN-, it upregulates other cytokines as TNF-, IL-8, and IL-10.
IL-17
Activated memory T-cells
(i) A proinflammatory cytokine, having a potential to modulate the MGIR to mastitis-causing pathogens. (ii) Appears to play an upstream role in T-cell-triggered inflammation by stimulating stromal cells to secrete other cytokines. (iii) Could play a role in the recruitment of neutrophils in the BMG during infection or immune-mediated inflammation through regulating IL-8. (iv) IL-17A, and to a lesser extent IL-17F, increase the expression of a number of genes encoding cytokines, chemokines, and proteins endowed with antibacterial activities. (v) Enhances expression of chemokines targeting neutrophils and mononuclear leucocytes. (vi) Enhances production of IL-6, IL-8, and Gro- and the expression of inflammatory cytokines TNF- and IL-1.
G-CSF
(i) Fibroblasts (ii) Endothelial cells (iii) Macrophages (iv) T-lymphocytes
(i) Increases numbers of both blood and milk neutrophils. (ii) Increases phagocytosis and bactericidal activity of leukocytes.
M-CSF
(i) Potent macrophage chemoattractant. (ii) Regulates proliferation and differentiation of macrophages.
GM-CSF
(i) Enhances chemotaxis and bactericidal activities of neutrophils. (ii) Increases number of phagocytic cells and enhances their cytotoxic activities.
IFN-
(i) T-lymphocytes, mainly Th1 and CD8+/T cytotoxic subset (ii) NK cells (iii) Monocytes
(i) Similar to IL-12, it serves to bridge the innate and adaptive arms of the IS. (ii) Mediates activation and microbicidal activity of neutrophils and macrophages. (iii) Reverses suppressive effects of MG secretions. (iv) Induces production of IL-12 by different phagocytes. (v) Upregulates cell-surface MHC-I molecule expression, thus promoting the induction of cell-mediated immunity by increasing the likelihood of cytotoxic T-cell recognition of presented Ags. (vi) Upregulates MHC-II Ag presentation pathway and corresponding CD4+ T-cell activation.
TNF-
(i) Macrophages (ii) Neutrophils (iii) MG epithelium
(i) The main cytokine produced during the early stage of infection. It enhances generation of febrile and acute phase inflammatory responses. (ii) Enhances neutrophil phagocytosis and bactericidal activity. (iii) Induces expression of adhesion molecules on endothelial cells. (iv) Stimulates secretion of IL-8 by different cells.
(i) A mediator of tissue repair and healing, MG epithelial proliferation, angiogenesis, and morphogenesis. (ii) Upregulates the production of prostaglandins and synergistically enhances the effects of IL-1 and TNF-. (iii) Stimulates IL-8, prostaglandin-E2, and expression of antimicrobial peptides.
TGF-
(i) Regulates ductal growth and patterning and alveolar development and functional differentiation. (ii) Exerts some pro- and anti-inflammatory properties. (iii) Induces extracellular matrix deposition and fibrosis after injury to the mammary epithelium, which contributes to the formation of scar tissue.
RANTES
(i) A member of the CC family of chemokines. It is involved in many immunoregulatory and inflammatory processes, though its exact roles during IMI are not clear. (ii) RANTES was found to be important for initiation of chemotaxis as well as maintenance of inflammation inside bovine MG.
