Prolonged perturbations of tumour necrosis factor-alpha and interferon-gamma in mice inoculated with Clostridium piliforme

Clostridium piliforme is an obligate intracellular bacterium that causes en terohepatic disease in many animal species. C. piliforme infections are com monly subclinical in laboratory rats and mice, and little is known about ho st regulation of disease or of the effects of C. piliforme infections on in vestigations that use subclinically infected animals. To assess host regula tion of subclinical C. piliforme infections and the effects of those infect ions on laboratory mice, the expression of the pro-inflammatory cytokines t umour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) wa s evaluated at 0, 1, 3, 7, 14 and 28 days after inoculation with C. pilifor me. Subclinical infection was induced in weanling C. piliforme-susceptible DBA/2 or -resistant C57BL/6 mice with either a toxic or a non-toxic C. pili forme strain. Hepatic lesions and bacteria were demonstrated histologically in both mouse strains for 14 days after inoculation with the toxigenic bac terial strain, but were never demonstrated histologically following inocula tion with the non-toxigenic strain. Hepatic TNF-alpha and IFN-gamma mRNA an d serum protein levels were similarly elevated ill both mouse strains 1 day after inoculation with both C. piliforme strains, as evaluated by reverse transcription PCR and enzyme-linked immunosorbent assays, respectively. Ele vation of IFN-gamma persisted for 14 days after inoculation; TNF-alpha rema ined elevated at 28 days after inoculation.