Biomedical subjects

Ian Kimber

Publications and source records attributed to Ian Kimber.

77 records · Page 5Linked to original sources

PubMedDate not supplied

Interleukins 5 and 13 characterize immune responses to respiratory sensitizing acid anhydrides.

There is some debate regarding whether occupational asthma induced by respiratory sensitizing acid anhydrides is mediated by the induction of T helper (Th) 2-type responses and the production of IgE, with failure to detect specific IgE antibody in some symptomatic patients. In the current investigations, cytokine secretion profiles induced in draining lymph node cells (LNC) by topical application to BALB/c strain mice of trimellitic anhydride (TMA), phthalic anhydride (PA) and maleic anhydride (MA) have been examined. Responses were compared with those induced by exposure to 2,4-dinitrochlorobenzene (DNCB), a contact allergen that lacks respiratory sensitizing potential. Exposure to all three acid anhydrides stimulated vigorous expression of interleukin (IL)-5, IL-10 and IL-13 but relatively low levels of the type 1 cytokines interferon-gamma (IFN-gamma) and IL-12. In addition, TMA-activated LNC expressed high levels of mitogen-inducible IL-4 whereas MA and PA displayed a lesser potential to elaborate this cytokine. The DNCB-stimulated LNC exhibited the converse type 1 phenotype of cytokine expression. The CD4(+) Th2 cells were the primary source of type 2 cytokines. Respiratory sensitizing acid anhydrides induce a predominantly Th2 cytokine phenotype, including the expression of IL-5 and IL-13, cytokines which in the presence of only very low levels of IL-4 may provide for an IgE-independent mechanism for the development of chemical respiratory allergy. These data provide additional support for the use of cytokine secretion profiling for the prospective identification of chemical respiratory allergens.

Allergens↗

PubMedDate not supplied

Assessment of the skin sensitization potency of eugenol and its dimers using a non-radioisotopic modification of the local lymph node assay.

Allergic contact dermatitis is a serious health problem. There is a need to identify and characterize skin sensitization hazards, particularly with respect to relative potency, so that accurate risk assessments can be developed. For these purposes the murine local lymph node assay (LLNA) was developed. Here, we have investigated further a modi fi cation of this assay, non-radioisotopic LLNA, which in place of tritiated thymidine to measure lymph node cell proliferation employs incorporation of 5-bromo-2'-deoxyuridine. Using this method we have examined the skin sensitizing activity of eugenol, a known human contact allergen, and its dimers 2,2'-dihydroxyl-3,3'-dimethoxy-5,5'-diallyl-biphenyl (DHEA) and 4,5'-diallyl-2'-hydroxy-2,3'-dimethoxy phenyl ether (DHEB). Activity in the guinea pig maximization test (GPMT) also measured. On the basis of GPMT assays, eugenol was classified as a mild skin sensitizer, DHEA as a weak skin sensitizer and DHEB as an extreme skin sensitizer. In the non-radioisotopic LLNA all chemicals were found to give positive responses insofar as each was able to provoke a stimulation index (SI) of >or=3 at one or more test concentrations. The relative skin sensitizing potency of these chemicals was evaluated in the non-radioisotopic LLNA by derivation of an ec(3) value (the concentration of chemical required to provoke an SI of 3). The ec(3) values calculated were 25.1% for eugenol, >30% for DHEA and 2.3% for DHEB. Collectively these data suggest that assessments of relative potency deriving from non-radioisotopic LLNA responses correlate well with evaluations based on GPMT results. These investigations provide support for the proposal that the non-radioisotopic LLNA may serve as an effective alternative to the GPMT where there is a need to avoid the use of radioisotopes.

Allergens↗

PubMedDate not supplied

Epidermal Langerhans cell migration and sensitisation to chemical allergens.

Epidermal Langerhans cells (LC) form part of the wider family of dendritic cells (DC; professional antigen-processing and antigen-presenting cells). LC are considered to serve in the skin as sentinels of the adaptive immune system, surveying the local environment and transporting foreign antigen for presentation to responsive T lymphocytes in regional lymph nodes. As such, LC play pivotal roles in the initiation of cutaneous immune responses, including immune responses to chemical allergens encountered at skin surfaces. Here we explore two aspects of LC function in the context of sensitisation to chemical allergens. The first is consideration of the cytokine and chemokine signals that regulate and counter-regulate the mobilisation and migration of LC from the epidermis to skin-draining lymph nodes following topical sensitisation. The second is examination of the ways in which LC may influence the polarity of induced T lymphocytes, and thereby the quality of immune responses.

Allergens↗

PubMedDate not supplied

Immune responses: adverse versus non-adverse effects.

The adaptive immune system in vertebrates has evolved to provide host resistance to infectious microorganisms and malignant disease. Normal immune function and the induction of specific immune responses require the orchestrated interaction between cells and molecules both within and outside the lymphoid system. Immunotoxicology can be defined as the study of adverse health effects that may result from the interaction of xenobiotics with the immune system. In general terms such effects can take one of two forms. The first of these is immunotoxicity (or immunosuppression) where there is a perturbation of, or damage to, one or more components of the immune system resulting in impaired immune function and reduced host resistance. The design and interpretation of experimental immunotoxicity studies and the investigation of clinical immunosuppression require consideration of the relationship between changes in the structure and/or function of discrete components of the immune system and holistic changes in the susceptibility to infectious and malignant disease. The other main way in which chemicals may cause adverse health effects secondary to interaction with the immune system is through stimulation of specific immune responses that result in allergic disease. Allergy to chemicals and proteins can take many forms, including allergic contact dermatitis, allergic sensitization of the respiratory tract (associated with rhinitis and/or asthma), systemic allergic reactions (associated frequently with drug treatment), and gastrointestinal disease. Here there is a need to distinguish between immunogenic responses per se and those immune responses that are of sufficient vigor and of the quality necessary to provoke allergic sensitization. The purpose of this article is to explore the extent to which distinctions can be drawn between adverse and nonadverse effects in the context of immunotoxicity and allergy.

Animals↗

PubMedDate not supplied

Reduction, refinement and replacement: putting the immune system to work.

Many chemicals are known to be, or have been implicated as, contact allergens, and allergic contact dermatitis is an important occupational and environmental health issue. It is the responsibility of toxicologists to identify those chemicals that have the potential to induce skin sensitisation, and to assess the conditions under which there will exist a risk to human health. This article describes progress that has been made in the development of new approaches to the toxicological evaluation of skin sensitisation, and the benefits to animal welfare that such developments have already produced, and are likely to produce in the future. In this context, the local lymph node assay is described with regard to hazard identification and risk assessment, and possible strategies for the development of in vitro approaches to safety assessment are discussed.

Allergens↗