TY - JOUR

T1 - Systemic immunogenicity of para-Phenylenediamine and Diphenylcyclopropenone

T2 - two potent contact allergy-inducing haptens

AU - Svalgaard, Jesper Dyrendom

AU - Særmark, Carina

AU - Dall, Morten

AU - Buschard, Karsten

AU - Johansen, Jeanne D

AU - Engkilde, Kåre

PY - 2014/1

Y1 - 2014/1

N2 - p-Phenylenediamine (PPD) and Diphenylcyclopropenone (DPCP) are two potent haptens. Both haptens are known to cause delayed-type hypersensitivity, involving a cytokine response and local infiltration of T-cell subpopulations, resulting in contact dermatitis. We investigated the systemic immune effects of PPD and DPCP, two relatively unexplored skin allergens. The dorsal sides of the ears of BALB/c mice were exposed to PPD or DPCP (0.1% w/v or 0.01% w/v), or vehicle alone. Mice were treated once daily for 3 days (induction period) and subsequently twice per week for 8 weeks. Local and systemic immune responses in the auricular and pancreatic lymph nodes, spleen, liver, serum, and ears were analyzed with cytokine profiling MSD, flow cytometry, and qPCR. Ear swelling increased significantly in mice treated with 1% PPD, 0.01% DPCP or 0.1% DPCP, compared with vehicle treatment, indicating that the mice were sensitized and that there was a local inflammation. Auricular lymph nodes, pancreatic lymph nodes, spleen, and liver showed changes in regulatory T-cell, B-cell, and NKT-cell frequencies, and increased activation of CD8(+) T cells and B cells. Intracellular cytokine profiling revealed an increase in the IFN-γ- and IL-4-positive NKT cells present in the liver following treatment with both haptens. Moreover, we saw a tendency toward a systemic increase in IL-17A. We observed systemic immunological effects of PPD and DPCP. Furthermore, concentrations too low to increase ear thickness and cause clinical symptoms may still prime the immune system. These systemic immunological effects may potentially predispose individuals to certain diseases.

AB - p-Phenylenediamine (PPD) and Diphenylcyclopropenone (DPCP) are two potent haptens. Both haptens are known to cause delayed-type hypersensitivity, involving a cytokine response and local infiltration of T-cell subpopulations, resulting in contact dermatitis. We investigated the systemic immune effects of PPD and DPCP, two relatively unexplored skin allergens. The dorsal sides of the ears of BALB/c mice were exposed to PPD or DPCP (0.1% w/v or 0.01% w/v), or vehicle alone. Mice were treated once daily for 3 days (induction period) and subsequently twice per week for 8 weeks. Local and systemic immune responses in the auricular and pancreatic lymph nodes, spleen, liver, serum, and ears were analyzed with cytokine profiling MSD, flow cytometry, and qPCR. Ear swelling increased significantly in mice treated with 1% PPD, 0.01% DPCP or 0.1% DPCP, compared with vehicle treatment, indicating that the mice were sensitized and that there was a local inflammation. Auricular lymph nodes, pancreatic lymph nodes, spleen, and liver showed changes in regulatory T-cell, B-cell, and NKT-cell frequencies, and increased activation of CD8(+) T cells and B cells. Intracellular cytokine profiling revealed an increase in the IFN-γ- and IL-4-positive NKT cells present in the liver following treatment with both haptens. Moreover, we saw a tendency toward a systemic increase in IL-17A. We observed systemic immunological effects of PPD and DPCP. Furthermore, concentrations too low to increase ear thickness and cause clinical symptoms may still prime the immune system. These systemic immunological effects may potentially predispose individuals to certain diseases.

KW - Animals

KW - B-Lymphocytes

KW - Cyclopropanes

KW - Cytokines

KW - Dermatitis, Allergic Contact

KW - Ear, External

KW - Female

KW - Flow Cytometry

KW - Lymph Nodes

KW - Mice

KW - Mice, Inbred BALB C

KW - Phenylenediamines

KW - RNA

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - T-Lymphocytes, Regulatory

U2 - 10.1007/s12026-013-8482-z

DO - 10.1007/s12026-013-8482-z

M3 - Journal article

C2 - 24385090

VL - 58

SP - 40

EP - 50

JO - Immunologic Research

JF - Immunologic Research

SN - 0257-277X

IS - 1

ER -