Nickel, cobalt, chromium, palladium and gold induce a mixed Th1- and Th2-type cytokine response in vitro in subjects with contact allergy to the respective metals - PubMed
Nickel, cobalt, chromium, palladium and gold induce a mixed Th1- and Th2-type cytokine response in vitro in subjects with contact allergy to the respective metals
J T Minang et al. Clin Exp Immunol. 2006 Dec.
Abstract
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)-gamma] 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-gamma) (all P < 0.05) and Ni (all four cytokines; P < 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.
Figures

Nickel (Ni), cobalt (Co), chromium (Cr), palladium (Pd), and gold (Au) induce a similar, mixed Th1-/Th2-type cytokine response in peripheral blood mononuclear cells (PBMC) from metal allergic subjects. PBMC from patch test positive or control subjects were incubated in the absence or presence of the metal to which the subject is reactive in the patch test. Interleukin (IL)-2, IL-13 and interferon (IFN)-γ production and the number of IL-2-, IL-4- and IL-13-producing cells were determined by enzyme-linked immunosorbent assay (ELISA) (y-axis on the left) and enzyme-linked immunospot assay (ELISpot) (y-axis on the right), respectively. Plots show spontaneous cytokine production in the absence of metal stimuli and production induced by metals. Shown are responses to Ni (donor 1), Co (donor 5), Cr (donor 15), Pd (donor 13) and Au (donor 26), see Table 1. The metal to which each subject reacted in the patch test, and which was used for in vitro stimulation, is indicated. For comparison, the responses (mean and standard deviation) of the non-allergic control subjects (n = 5) are shown on the right panel of each plot.

Profile of cytokine responses to nickel (Ni), cobalt (Co), chromium (Cr), palladium (Pd) and gold (Au) in metal patch test positive and control subjects. Peripheral blood mononuclear cells (PBMC) from metal patch test positive (Ni, n = 17; Co, n = 12; Cr, n = 9; Pd, n = 4; Au, n = 10) or control (n = 5) subjects were incubated in the absence or presence of the metal(s) to which each metal allergic subject is reactive in the patch test. Interleukin (IL)-2, IL-13 and interferon (IFN)-γ production and the number of IL-2-, IL-4- and IL-13-producing cells were measured by enzyme-linked immunosorbent assay (ELISA) (left panel) and enzyme-linked immunospot assay (ELISpot) (right panel), respectively. Shown are data after subtraction of spontaneous background with the median response for each group indicated within the boxes (grey boxes for metal patch test positive subjects; open boxes for patch test negative non-allergic controls). The top and bottom ends of each box represent the 75th and 25th percentiles, respectively, while the top and bottom bars indicate the maximum and minimum values in the data set. The statistical differences between the groups following a Mann–Whitney U-test are depicted with asterisks (*P < 0·05; **P < 0·01; ***P < 0·001).
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