Cytokine endpoints for the local lymph node assay: consideration of interferon‐γ and interleukin 12

The murine local lymph node assay (LLNA) is a method for the prospective identification of contact allergens. Skin sensitization potential is assessed as a function of induced proliferative responses in lymph nodes draining the site of topical exposure measured in situ by incorporation of radiolabelled thymidine ([3H]thymidine). The results of previous investigations have demonstrated that the analysis of [3H]thymidine incorporation represents a robust and reliable endpoint for the LLNA for the assessment of skin sensitizing activity for strong and moderate allergens and, in addition, many weaker sensitizers. The aim of the current experiments was to explore the utility of the production of the cytokines interferon‐γ (IFN‐γ) and interleukin 12 (IL‐12) by draining lymph node cells (LNC) as alternative readouts for the LLNA.

[1]  D. Basketter,et al.  Interlaboratory Evaluation of the Local Lymph Node Assay with 25 Chemicals and Comparison with Guinea Pig Test Data , 1991 .

[2]  D. Basketter,et al.  The performance of the local lymph node assay with chemicals identified as contact allergens in the human maximization test. , 1994, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[3]  T. Germann,et al.  Differential expression of mRNA encoding interleukin‐12 p35 and p40 subunits in situ , 1994, European journal of immunology.

[4]  D. Basketter,et al.  Classification of Chemical Allergens According to Cytokine Secretion Profiles of Murine Lymph Node Cells , 1997, Journal of applied toxicology : JAT.

[5]  I Kimber,et al.  Investigation of lymph node cell proliferation as a possible immunological correlate of contact sensitizing potential. , 1991, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[6]  Ian Kimber,et al.  Interleukin 6 (IL-6) Production by Lymph Node Cells: An Alternative Endpoint for the Murine Local Lymph Node Assay , 1993 .

[7]  G. Trinchieri,et al.  The role of interleukin 12 in the immune response, disease and therapy. , 1994, Immunology today.

[8]  I Kimber,et al.  The local lymph node assay: developments and applications. , 1994, Toxicology.

[9]  D. Basketter,et al.  Differential cytokine production following chronic exposure of mice to chemical respiratory and contact allergens. , 1995, Immunology.

[10]  I Kimber,et al.  The murine local lymph node assay: a commentary on collaborative studies and new directions. , 1992, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[11]  I. Kimber,et al.  The local lymph node assay: Results of a final inter‐laboratory validation under field conditions , 1992, Journal of applied toxicology : JAT.

[12]  J Hilton,et al.  Further evaluation of the local lymph node assay in the final phase of an international collaborative trial. , 1996, Toxicology.

[13]  D. Basketter,et al.  The local lymph node assay: An interlaboratory evaluation of Interleukin 6 (IL‐6) production by draining lymph node cells , 1994, Journal of applied toxicology : JAT.

[14]  Kimber,et al.  Comparison of cytokine secretion profiles provoked in mice by glutaraldehyde and formaldehyde , 1999, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[15]  J Hilton,et al.  An international evaluation of the murine local lymph node assay and comparison of modified procedures. , 1995, Toxicology.

[16]  D. Basketter,et al.  Characterization of chemical allergens as a function of divergent cytokine secretion profiles induced in mice. , 1996, Toxicology and applied pharmacology.

[17]  I. Kimber,et al.  Identification of contact allergens using the murine local lymph node assay: Comparisons with the buehler occluded patch test in guinea pigs , 1990, Journal of applied toxicology : JAT.

[18]  Maguire Hc Murine Recombinant lnterleukin-12 Increases the Acquisition of Allergic Contact Dermatitis in the Mouse , 1995 .

[19]  D. Holder,et al.  Evaluation of lymphocyte proliferation by immunohistochemistry in the local lymph node assay , 1995, Journal of applied toxicology : JAT.

[20]  A. Sher,et al.  Diversity of Cytokine Synthesis and Function of Mouse CD4+ T Cells , 1991, Immunological reviews.

[21]  D A Basketter,et al.  Comparison of the local lymph node assay with the guinea-pig maximization test for the detection of a range of contact allergens. , 1992, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[22]  D. Carvajal,et al.  IL-12-Deficient Mice Are Defective in IFNγ Production and Type 1 Cytokine Responses , 1996 .

[23]  J Hilton,et al.  Assessment of the skin sensitization potential of topical medicaments using the local lymph node assay: an interlaboratory evaluation. , 1998, Journal of toxicology and environmental health. Part A.

[24]  T. Mosmann,et al.  The role of IFN-gamma in delayed-type hypersensitivity mediated by Th1 clones. , 1989, Journal of immunology.

[25]  S Kato,et al.  A modification of the local lymph node assay for contact allergenicity screening: measurement of interleukin-2 as an alternative to radioisotope-dependent proliferation assay. , 1995, Toxicology.

[26]  Ian Kimber,et al.  Contact sensitization: A new approach to risk assessment , 1997 .

[27]  D. Basketter,et al.  Selective induction of type 2 cytokines following topical exposure of mice to platinum salts. , 1998, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[28]  G. Trinchieri,et al.  Neutralization of IL-12 in vivo prevents induction of contact hypersensitivity and induces hapten-specific tolerance. , 1996, Journal of immunology.

[29]  G. Trinchieri,et al.  Interleukin-12: a cytokine produced by antigen-presenting cells with immunoregulatory functions in the generation of T-helper cells type 1 and cytotoxic lymphocytes. , 1994, Blood.

[30]  I Kimber,et al.  The local lymph node assay: a viable alternative to currently accepted skin sensitization tests. , 1996, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[31]  T. Gray,et al.  The murine local lymph node assay: results of an inter-laboratory trial. , 1991, Toxicology letters.

[32]  Baohui Xu,et al.  In Vitro Evaluation of Contact Sensitivity to DNCB Using Hapten-Stimulated in Vitro Interleukin-2 Production by Murine Lymph Node Cells , 1993 .

[33]  B. Homey,et al.  A modified murine local lymph node assay for the differentiation of contact photoallergy from phototoxicity by analysis of cytokine expression in skin-draining lymph node cells. , 1998, Toxicology.