Sulfasalazine attenuates staphylococcal enterotoxin B-induced immune responses

Abstract

Staphylococcal enterotoxin B (SEB) and related exotoxins are important virulence factors produced by Staphylococcus aureus as they cause human diseases such as food poisoning and toxic shock. These toxins bind directly to cells of the immune system resulting in hyperactivation of both T lymphocytes and monocytes/macrophages. The excessive release of proinflammatory cytokines from these cells mediates the toxic effects of SEB. This study examined the inhibitory activities of an anti-inflammatory drug, sulfasalazine, on SEB-stimulated human peripheral blood mononuclear cells (PBMC). Sulfasalazine dose-dependently inhibited tumor necrosis factor α, interleukin 1 (IL-1) β, IL-2, IL-6, interferon γ (IFNγ), and various chemotactic cytokines from SEB-stimulated human PBMC. Sulfasalazine also potently blocked SEB-induced T cell proliferation and NFκB activation. These results suggest that sulfasalazine might be useful in mitigating the toxic effects of SEB by blocking SEB-induced host inflammatory cascade and signaling pathways.

Figure 1

Dose-response inhibition of (A) interleukin 1β (IL-1β), tumor necrosis factor α (TNFα), and IL-6; (B) interferon γ (IFNγ) and IL-2; (C) monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein (MIP)-1α, MIP-1β production by peripheral blood mononuclear cells (PBMC) stimulated with 200 ng/mL of staphylococcal enterotoxin B (SEB) in the presence of various concentrations of sulfasalazine (SFZ). Values represent the mean ± SD of duplicate samples and results represent three experiments. Results are statistically significant (p < 0.05) between SEB and SEB plus SFZ samples at concentrations of 0.25 and 1.25 mM.

Figure 1

Dose-response inhibition of (A) interleukin 1β (IL-1β), tumor necrosis factor α (TNFα), and IL-6; (B) interferon γ (IFNγ) and IL-2; (C) monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein (MIP)-1α, MIP-1β production by peripheral blood mononuclear cells (PBMC) stimulated with 200 ng/mL of staphylococcal enterotoxin B (SEB) in the presence of various concentrations of sulfasalazine (SFZ). Values represent the mean ± SD of duplicate samples and results represent three experiments. Results are statistically significant (p < 0.05) between SEB and SEB plus SFZ samples at concentrations of 0.25 and 1.25 mM.

Figure 2

Inhibition of T-cell proliferation in PBMC stimulated with 200 ng/mL of SEB. Values represent the mean ± SD of triciplate samples and results represent three experiments. Results are statistically significant (p < 0.05) between SEB and SEB plus SFZ samples at concentrations of 0.25 and 1.25 mM.

Figure 3

Inhibition of NF-κB activation in PBMC stimulated with 200 ng/mL of SEB. Values represent the mean ± SD of duplicate samples and results represent two experiments.