Immunomodulatory effects of environmental xenobiotics and biotic factors on the populations of mouse-like rodents

The research goal of the Project is to investigate the immunomodulatory potential of selected environmental chemical agents – the heavy metal cadmium and the rodenticide warfarin. The effects of these xenobiotics will be assessed by changes in the cellular and molecular immune mechanisms in laboratory rats exposed to these agents in relation to: 1. Duration of exposure (acute or subchronic application régime); 2. Physiological factors that modulate the immune function, such as genetic background (strain) of rats; and 3. The action of these xenobiotics on the induction of the immune response. The effects of different application régimes will be investigated in individuals of two highly inbred rat strains, known to demonstrate quantitative and/or qualitative differences in their immune responses to chemical and biological agents, both (a) under basal conditions of immune system function and (b) under conditions of immune response induction, in contact hypersensitivity reaction to the hapten dinitrochlorobenzene (for warfarin) and in pulmonary infection by an ubiquitous biotic agent, the fungus Aspergillus fumigatus (for cadmium). The investigation of the effects of warfarin and cadmium, dependent on exposure duration and in relation to the influence of genetic background, under basal conditions of immune system function as well as during the induction of immune responses, may provide new data regarding the mechanisms of action of these xenobiotics on the immune system.