The immunotoxicological pattern of subchronic and chronic benzene exposure in rats

•Benzene and its metabolites cause hypocellularity in central and peripheral immune organs.•Total WBCs and lymphocyte counts decrease with increasing duration of benzene exposure.•Benzene exposure decreases CD4 + T cells, CD4+/CD8+ ratio and CD3+ T cells.•Con A induced splenocytes are characterized by increased IL-4 and decreased IL-6 release.•45-days benzene exposure is the most sensitive time point for benzene cytotoxicity.

Exposure to benzene and its inevitable metabolites can result in deleterious effects on human health, including lymphocytopenia, hematotoxicity and cancer. However, the duration of exposure might alter the effects including immune consequences. The aim of this study was to determine whether benzene could modulate lymphocyte proliferation induced by the T cell mitogen concanavalin A, in rats, at different exposure durations. 386 Wistar rats were assigned into control and treatment groups which were subdivided into groups for 45, 90 and 135 days for 0,6 mL/kg of drinking water mixed benzene treatment. The percentage of CD3+, CD4+, CD8+ spleen lymphocytes was defined using the flow cytometer. Interleukin (IL)-4, IL-6, IL-10 and interferon-gamma, in supernatants of splenocyte cultures stimulated with Concanavalin A, were assessed by enzyme-linked immunosorbent assay (ELISA) technique. The decrease in the total lymphocyte and T cell counts were associated with increased benzene exposure duration. Th2-type cytokine, IL-4 significantly increased, whereas IL-6, CD4 + T cells, CD4+/CD8+ ratio and CD3+ T cells decreased. Despite the positive correlation between benzene toxicity and indicated increased immune responses, 45-day exposure to benzene appeared to be the most sensitive time point for evaluating benzene cytotoxicity.