The skin is a direct target of the air pollutant benzo[a]pyrene (BaP). While its carcinogenic qualities are well-studied, the immunotoxicity of BaP after dermal exposure is less understood. This study examines the immunomodulatory effects of a 10-day epicutaneous BaP application, in environmentally/occupationally relevant doses, by analyzing ex vivo skin immune response (skin explant, epidermal cells and draining lymph node/DLN cell activity), alongside the skin’s reaction to sensitization with experimental hapten dinitrochlorobenzene (DNCB). The results show that BaP application disrupts the structure of the epidermal layer and promotes immune cell infiltration in the dermis. BaP exposure led to oxidative stress in epidermal cells, characterized by decreased reduced glutathione and increased AHR and Cyp1A1 expression. Production and gene expression of proinflammatory cytokines (TNF, IL-1β) by epidermal cells decreased, while IL-10 response increased. Decreased spontaneous production of IFN-γ and IL-17, along with unchanged IL-10, was observed in DLC cells, whereas ConA-stimulated production of these cytokines was elevated. Local immunosuppression caused by BaP application seems to reduce the skin’s response to an additional stimulus, evidenced by decreased effector activity of DLN cells three days after sensitization with DNCB. These findings provide new insight into the immunomodulatory effects and health risks associated with skin exposure to BaP.

Purpose: The efficacy of topical dinitrochlorobenzene (DNCB) in the treatment of some skin dermatoses is based both on local and systemic effects. It is not known, however, whether it can be applied to patients receiving some other therapy associated with systemic immunomodulation. The aim of the present paper using a rat model was to examine whether oral warfarin (WF) intake, as shown by others and by us, had an immunomodulatory potential to interfere with effects of topical DNCB as systemic immunotherapy. Materials and methods: Rats received 3.5 mg/l of WF sodium in drinking water for 30 days and were thereafter skin-sensitized with 0.4% DNCB. Changes in the oxidative activity (myeloperoxidase/MPO, reduction of nitroblue tetrazolium/NBT and nitric oxide/NO production) as well as tumor necrosis factor (TNF) production by peripheral blood polymorphonuclear cells (PMN) were measured and compared with PMN from sensitized unexposed to WF rats. Results: WF intake enhanced some aspects of PMN activity (intracellular MPO activity and unstimulated NO production) as well as their responsiveness to exogenous stimulation (NBT reduction and TNF production from sensitized animals). However, WF also decreased PMN responsiveness of NO production to stimulation. WF affected NO and TNF production solely by PMN, as no effect on these activities of peripheral blood mononuclear cells was seen. Conclusion: Having in mind that polymorphonuclear leukocytes are the most abundant cell type in peripheral blood in humans, increase of basic aspects of PMN activity described in the present paper might be relevant for consideration of using WF as therapeutic modality in patients topically treated with DNCB.

Inflammatory/immune cells and mediators are substantial for wound healing because they orchestrate biological activities in this complex process. Among factors that affect wound healing, obesity, and metabolic diseases are among the most significant, particularly because of a relationship between obesity and a prediabetic state with immune reactivity. Using Dark Agouti (DA) and Albino Oxford (AO) rats, which differ in immune responses as well as in proneness to obesity, we examined the impact of these intrinsic factors on cutaneous wound healing. Dynamics of the process were monitored at days 3, 5, and 7 post‐wounding parallel in both rat strains by analysis of selected basic aspects of the wound repair process (cytokine and growth factor responses) in granulation tissue. Strain‐related differences in the extent of reduction of the wound area were shown, which coincided with differential proinflammatory and immune‐regulatory cytokines, as well as growth factors response in these rats. Some of these differences seem related to their dissimilarities in the proneness to obesity. Results in this study extended so far known differences in inflammatory/immune responses to a variety of stimuli between AO and DA rats and showed, for the first time, immune‐based differences in wound healing between rats that differ in body mass (BM) and obesity proneness (under ad libitum feeding conditions with normal rodent chow).