Oral cadmium increases contact hypersensitivity reaction in rats

Abstract

Cadmium (Cd) in food and drinking water presents a health risk to the general population. We have shown previously that orally‐acquired Cd affects basal immune homeostasis in the skin. In this study, we examined the effect of 30‐days oral exposure of inflammatory disease‐prone Dark Agouti (DA) rats to two environmentally relevant Cd doses (5 and 50 ppm) on contact hypersensitivity reaction (CHS) induced by topical 0,4% dinitrochlorobenzene (DNCB). Both Cd doses increased proinflammatory epidermal cell response (IL‐1, TNF and IL‐6 production) to DNCB sensitization, as well as epidermal cells’ potential to stimulate naïve lymphocytes ex vivo (increased IFN‐γ and IL‐17 production in co‐cultures). The proinflammatory milieu of epidermal cells induced by sensitization was accompanied by increased hapten‐specific production of IFN‐γ (at a lower Cd dose) and IL‐17 (at both Cd doses) by draining lymph node (DLN) cells, compared to Cd non‐treated animals. During the challenge phase of CHS, oral Cd increased ear swelling response and skin inflammation (edema, mononuclear and neutrophil cell infiltration) at both Cd doses, what correlated with increased innate (TNF) and hapten‐specific effector (IFN‐γ, IL‐17) cytokine response by ear cells. Even in Albino Oxford (AO) rats generally less prone to inflammation, oral Cd increased the proinflammatory response of epidermal cells following sensitization, however, DLN cell responses were absent. Ear swelling response to hapten challenge was observed in AO individuals which acquired a higher Cd dose. Presented data imply the potential of food‐ and water‐borne Cd to be risk factors for skin disease development and/or its exacerbation.