Caspase inhibitors attenuate superantigen-induced inflammatory cytokines, chemokines, and T-cell proliferation

Abstract

Proinflammatory cytokines mediate the toxic effect of superantigenic staphylococcal exotoxins (SE). A pan-caspase inhibitor suppressed SE-stimulated T-cell proliferation and the production of cytokines and chemokines by human peripheral blood mononuclear cells. These data suggest that caspase inhibitors may represent a novel therapeutic modality for treating SE-induced toxic shock.

FIG. 1.

Dose-response inhibition of IL-1β, IL-6, and TNF-α (A); IFN-γ (B); and MCP-1, MIP-1α, and MIP-1β (C) production by PBMC stimulated with 200 ng of SEB/ml in the presence of various concentrations of Z-D-CH2-DCB. Values are the means ± standard deviations (SD) of values for duplicate samples from three experiments.

FIG. 2.

Inhibition of IL-1β, IL-6, TNF-α, and IFN-γ (A) and MCP-1, MIP-1α, and MIP-1β (B) production by PBMC stimulated with 200 ng of SEB or TSST-1 per ml in the presence of a 100 μM concentration of the caspase inhibitors indicated. Values are the means ± SD of results from PBMC cultures from six blood donors. ZDCH2, Z-D-CH₂-DCB; ZVAD, Z-VAD-fmk; AcYVAD Ac-YVAD-cmk.

FIG. 3.

Inhibition of T-cell proliferation in PBMC stimulated with 200 ng of SEB/ml by various concentrations of caspase inhibitors. Values are the mean counts ± SD of results from triplicate cultures from three experiments.