Evidence for Clostridium perfringens Enterotoxin (CPE) Inducing a Mitogenic and Cytokine Response In Vitro and a Cytokine Response In Vivo

摘要

We investigated some immunogenic properties of Clostridium perfringens enterotoxin (CPE) in vitro using murine J774A macrophages (M#PHI#) and in vivo using Swiss Webster (SW) mice. CPE was a potent mitogen in vitro, where cell proliferation increased with CPE concentration. CPE was nonmitogenic when M#PHI# were concurrently incubated with CPE and interferon gamma (IFN-#gamma#). M#PHI# incubated in the presence of CPE induced the synthesis of interleukin-l (lL-1), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-#alpha#) and interferon-gamma (IFN-#gamma#), but not interleukin-2 (IL-2). In vivo, CPE induced a pro-inflammatory cytokine response with striking production of IFN-#gamma#, IL-1, and IL-6. Regardless of route of CPE entry, serum cytokine levels generally peaked within 1 h of administration and were maintained for 4-8 h. Although CPE engenders an intense immune response during toxicosis, the toxin does not appear to be a superantigen. Death from CPE-induced shock appears to result from various interrelating immunological mechanisms.