Nickel, cobalt, chromium, palladium and gold induce a mixed Th1- and Th2-type cytokine response<i>in vitro</i>in subjects with contact allergy to the respective metals

TLDR

Nickel is the main metal allergen that induces both Th1 and Th2 cytokine production in peripheral blood mononuclear cells of allergic individuals. The study aimed to characterize the cytokine responses of PBMCs from patients sensitized to nickel, cobalt, chromium, palladium, and gold. PBMCs from 31 allergic patients and 5 controls were stimulated with the corresponding metal salts and cytokine production (IL‑2, IFN‑γ, IL‑4, IL‑13) was quantified by ELISpot and ELISA. All five metals triggered a mixed Th1/Th2 cytokine profile in allergic PBMCs but not in controls, with significant elevations for Cr, Pd, Au, and Ni, and 71 % of positive and 89 % of negative patch tests were reflected in vitro, indicating that sensitization to these metals elicits a similar mixed Th1/Th2 response as nickel.

Abstract

Summary Nickel (Ni), the main cause of contact allergy to metals, induces in vitro production of both Th1- and Th2-type cytokines in peripheral blood mononuclear cells (PBMC) from allergic subjects. Because the knowledge of the cellular immune response to other metals involved in contact allergy has been limited, we investigated the cytokine profile induced by Ni, cobalt (Co), chromium (Cr), palladium (Pd) and gold (Au) in PBMC from patients with patch test reactivity to the respective metals. PBMC from patients with patch test reactivity to Ni, Co, Cr, Au and/or Pd (n = 31) and non-allergic controls (n = 5) were stimulated in vitro with corresponding metal salts. Th1- [interleukin (IL)-2 and interferon (IFN)-γ] and Th2- (IL-4 and IL-13) type cytokine responses were measured by enzyme-linked immunospot (ELISpot) and/or enzyme-linked immunosorbent assay (ELISA). All metals induced a mixed Th1- and Th2-type cytokine production in PBMC from individual patients with patch test reactivity to the corresponding metal, but not in control PBMC. Significantly higher responses in the patient versus controls were found for Cr (IL-2 and IL-13), Pd (IL-2 and IL-4), Au (IL-13 and IFN-γ) (all P &amp;lt; 0·05) and Ni (all four cytokines; P &amp;lt; 0·01) but not Co. Overall, 71% (37/52) and 89% (81/91) of the positive and negative patch test reactivities to metals, respectively, were matched by the in vitro reactivity. In conclusion, our data suggest that sensitization to Co, Cr, Pd and Au results in a cellular immune response of a character similar to the mixed Th1- and Th2-type cytokine profile shown previously to be induced by Ni.