Early DNA Synthesis and Cytokine Expression in the Nickel Activation of Peripheral Blood Mononuclear Cells in Nickel-Allergic Subjects

• Published in: International archives of allergy and immunology Vol. 123; no. 2; pp. 170 - 176
• Main Authors: Falsafi-Amin, Hale, Lundeberg, Lena, Bakhiet, Moiz, Nordlind, Klas
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.10.2000; S. Karger AG
• Subjects: Adult; Aged; Allergic diseases; Biological and medical sciences; Cells, Cultured; Cytokines - analysis; Cytokines - biosynthesis; Dermatitis, Allergic Contact - etiology; Dermatitis, Allergic Contact - immunology; DNA - biosynthesis; Female; Humans; Immunopathology; Interleukin-2 - analysis; Interleukin-4 - analysis; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Lymphotoxin-alpha - analysis; Medical sciences; Medicin och hälsovetenskap; Middle Aged; nickel; Nickel - adverse effects; Original Paper; Skin allergic diseases. Stinging insect allergies; Time Factors; Contact allergy; Nickel; Proliferation; Cytokines; PBMC; Human; Allergy; Skin disease; Pathogenesis; Cytokine; Interleukin 4; Synthesis; Contact dermatitis; Interleukin 2; DNA; T-Lymphocyte; Tumor necrosis factor β; Female; ELISA assay; Allergen; Gamma interferon
• ISSN: 1018-2438; 1423-0097
• DOI: 10.1159/000024437

Background and Objective: Nickel sulphate stimulates the proliferation of lymphocytes in nickel-allergic subjects. However, nickel-induced stimulation of lymphocytes from control persons without clinical symptoms of nickel allergy has also been reported. The aim of the present study was to correlate T cell activity, measured by DNA synthesis and the expression of Th1 [interleukin (IL)-2, tumour necrosis factor (TNF)-β and interferon (IFN)-γ] and Th2 (IL-4) cytokines, in short-term (up to 72 h) culture of nickel-stimulated peripheral blood mononuclear cells (PBMC) from nickel-allergic patients compared to control subjects. Methods: DNA synthesis was measured by the incorporation of [methyl- 3 H]thymidine. The production of IL-2, TNF-β, IFN-γ and IL-4 was measured in the supernatants of the cultures by ELISA. In situ hybridization for mRNA was performed using oligonucleotide probes for IL-4, IFN-γ and TNF-β in cell smears. Results: Already after 24 h and proceeding through the remaining culture period, there was a statistically significant (p < 0.001) difference in the concentrations of IL-2 between patients and controls. There was a significant (p < 0.01) difference in DNA synthesis (stimulation index) between the patients and control subjects at 72 h, and also at the same time a difference in the concentrations of TNF-β (p < 0.05) and IL-4 (p < 0.01). In the in situ hybridization study, TNF-β was found to be the only one of the studied cytokines that differed between the nickel-allergic and control subjects, this difference being most evident at 72 h (p < 0.01). Conclusions: Our results indicate a difference between nickel-allergic and non-allergic subjects in the synthesis of DNA and production of cytokines when PBMC are stimulated by nickel sulphate, and IL-2 may be regarded as a critical and early-occurring cytokine