In vitro evaluation of interactions between cylindrospermopsin and water contaminants, arsenic and cadmium, in two human immune cell lines.

Cylindrospermopsin (CYN), a cyanotoxin with worldwide distribution, is gaining increased attention due to its bioaccumulation potential and toxicological effects. Previous research suggests that CYN may interact with other environmental contaminants, potentially amplifying its toxicity. To address this concern, the present study investigated the combined effects of CYN with arsenic (As) and cadmium (Cd) on human immune cell lines, Jurkat and THP-1. Cytotoxicity tests showed that As and Cd significantly decreased the viability of both cell lines after 24 and 48 h of exposure. The EC₅₀ (24 h) values for Jurkat cells were 13.15 ± 1.97 (As) and 36.92 ± 3.77μM (Cd), respectively, while for THP-1, the EC₅₀ (24 h) values were 46.48 ± 0.17 for As and 55.09 ± 4.98μM for Cd. Furthermore, individual contaminants and their mixtures with CYN impaired monocyte differentiation into macrophages. The effect on mRNA expression of some cytokines (TNF-α, INF-γ, IL-2, IL-6 and IL-8) was also assessed. In the Jurkat cell line, As upregulated IL-8 expression while Cd increased the expression of all interleukins. Exposure to binary combinations (CYN + As, and CYN + Cd) increased IL-2 and INF-γ expression. In THP-1 cells, As elevated IL-8 and INF-γ expression, whereas Cd caused an increase in TNF-α and INF-γ expression. Exposure to CYN + As up-regulated IL-8 and INF-γ expression, while the CYN + Cd combination down-regulated TNF-α expression. These findings highlight the complex interactions between contaminants, emphasizing the need for evaluating combined effects in risk assessments.