Evidence for Clostridium perfringens enterotoxin (CPE) inducing a mitogenic and cytokine response in vitro and a cytokine response in vivo

We investigated some immunogenic properties of Clostridirtm perfringens ent erotoxin (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 cel l proliferation increased with CPE concentration. CPE was nonmitogenic when Met were concurrently incubated with CPE and interferon gamma (IFN-gamma). M Phi incubated in the presence of CPE induced the synthesis of interleuki n-l (IL-1), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha) a nd interferon-gamma (IFN-gamma), but not interleukin-2 (IL-2). In vivo, CPE induced a pro-inflammatory cytokine response with striking production of I FN-gamma, IL-1 and IL-6. Regardless of route of CPE entry, serum cytokine l evels 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 sho ck appears to result from various interrelating immunological mechanisms.