Inflammatory cytokine

Source

Function

Response to Cd exposure

Interleukin-8

(IL-8)

Monocytes and macrophages [47]

Pro-inflammatory chemotactic factor that promotes the directional migration of neutrophils, basophils and T-lymphocytes [48]

↑ release in human astrocytes through MAPK phosphorylation [49]

↑ secretion by primary human airway epithelial cells in dose- and time-dependent manner independent of NF- κB [50]

Interleukin-6

(IL-6)

Macrophages, dendritic cells, T-cells, B-cells, endothelial cells, astrocytes, microglia and neurons [51]

Can have both pro-inflammatory and anti-inflammatory action depending on its level of expression [52]

Important in T-cell and B-cell differentiation as well as acute-phase response in liver [51]

↑ release in human astrocytes through MAPK phosphorylation and

activation of NF- κB [49]

↑ significant release in heart of male rats treated with 5 mg/kg b.w. for 4 weeks [53]

↑ secretion by primary human airway epithelial cells [50]

↓ secretion by murine macrophages treated with 0.1 µM and 10 µM Cd [54]

↑ levels in plasma of rats treated with 40 mg/L for 6 weeks [39]

Interleukin-1 beta (IL-1β)

Macrophages, microglia, B-cells, monocytes, fibroblasts and dendritic cells [51]

Pro-inflammatory mediator of innate immune response, critical for activation of macrophages and microglia, maturation of B-cell, stimulation of T-cells and

activation of natural killer cells [51]

$\leftrightarrow$ Secretion by murine macrophages treated with 0.1 µM Cd [54]

↑ secretion (3-fold) by murine macrophages treated with 10 µM Cd [54]

↓ mRNA expression but ↑ release in primary alveolar macrophages after Cd exposure [55]

Interleukin-10

(IL-10)

T-cells, monocytes, stimulated macrophages, subsets of dendritic cells, some granulocytes, epithelial cells and tumor cells [56]

Anti-inflammatory action by inhibiting the release of proinflammatory mediators [57]

↓ secretion by murine macrophages treated with 0.1 µM and 10 µM Cd [54]

Interleukin-17

(IL-17)

T-helper cells, mast cells, macrophages and eosinophils [51]

Pro-inflammatory cytokine involved in recruitment of intracellular adaptor proteins and downstream activation of NF-κB [58]

↑ mRNA levels with in protein product concentrations in spleen of rats [59]

Tumor necrosis factor-alpha

(TNF-α)

Activated macrophages in response to injurious stimuli [57]

Pro-inflammatory mediator of local and systemic inflammation by amplifying and prolonging inflammatory response by activating cells to release cytokines and mediators [57]

↑ significant release in heart of male rats treated with 5 mg/kg b.w. for 4 weeks [53]

↑ levels in plasma of rats treated with 40 mg/L for 6 weeks [39]

↓ mRNA expression but ↑ release in primary alveolar macrophages after Cd exposure [55]

Transforming growth factor-beta

(TGF-β)

Widely distributed including epithelial, endothelial, hematopoietic, neuronal and connective tissue cells [60]

Pro-fibrotic cytokine crucial in cell growth, apoptosis, differentiation, proliferation, migration, extracellular matrix production, immune regulation, wound healing and inflammation [60]

$\leftrightarrow$ mRNA levels in human bronchial cells treated with 10 µM Cd while

↓ mRNA levels in human bronchial cells treated with 20 µM Cd

↑ mRNA levels of receptors in human bronchial cells treated with 10 and 20 µM Cd [61]