Cytokine profiles in human exposure to metals (IUPAC Technical Report)

Abstract

Immunosensitization to metal ions through occupational and environmental exposure has been described in earlier papers from this project. Here we discuss the possible role of cytokine profiling in demonstrating and understanding this phenomenon. The cytokines are a large family of polypeptides exerting autocrine, paracrine, and/or endocrine effects. They include interleukins (ILs), interferons (IFNs), and growth factors. They may be grouped as pro-inflammatory (e.g., IL-1, IL-6, IL-12, IL-18, TNF-α), anti-inflammatory (e.g., IL-10), or those regulating T-helper (TH) cell function. The latter are subdivided into those associated with TH1 (e.g., IL-2, IL-12, IFN-γ, TNF-β) or TH2 (e.g., IL-4, IL-5, IL-13) cell function. Because different types of immune reactions (e.g., immediate reaction vs. delayed-type hypersensitivity) differentially involve TH1 and TH2 cells, measurement of cytokine production in response to metal ions can potentially give insight into underlying immune mechanisms and responses. Examples are given for species of Ni, Cr, Co, Hg, Cd, and Be; and in less detail for species of Fe, Pt, Pd, and Rh. Antibodies are available commercially that allow for the determination of many cytokines, and such measurements are most usefully performed with body fluids, supernatants from stimulated lymphocyte cultures, or lysates of lymphocytes or other biopsied cells. The predominant methods include enzyme-linked immunosorbent assay (ELISA) and flow cytometric measurement of the cytokine, bioassay of its activity in cell culture, and polymerase chain reaction (PCR) assessment of its mRNA level. In practice, levels of individual cytokines are highly variable between individuals, and reliable reference values are generally lacking. Ratios of cytokines are more informative than absolute concentrations, and biological variability in cytokine production dictates that repeated testing is necessary to confirm trends. Determining cytokine profiles is presently of questionable diagnostic utility in individual cases of metal sensitization, but is providing mechanistic insights in a research context.