Helicobacter pullorum outbreak in C57BL/6NTac and C3H/HeNTac barrier-maintained mice.

Helicobacter pullorum is a bacterial pathogen in humans. By using microaerobic culture techniques, H. pullorum was isolated from the feces of barrier-maintained mice and identified, on the basis of biochemical, restriction fragment length polymorphism, and 16S rRNA gene sequence analyses. This finding presents an opportunity to study H. pullorum pathogenesis in mice.

In lethally irradiated mice interleukin-12 protects bone marrow but sensitizes intestinal tract to damage from ionizing radiation.

Administration of IL-12 prior to lethal irradiation, protected a significant fraction of mice from 60Co-gamma radiation-induced lethal hematopoietic syndrome. Radioprotection was associated with an increase in the number of c-kit+ bone marrow cells (BMC) in IL-12 treated mice compared to saline-treated mice. Even after supralethal doses of radiation (1200 cGy), IL-12-treated mice had twofold greater numbers of c-kit+ BMC than controls. However the mice receiving IL-12 and 1200 cGy died of the gastrointestinal (GI) syndrome, evident by gross necroscopy and histological evaluation, within 4 to 6 days after irradiation. Induction of the GI syndrome in mice not treated with IL-12 required radiation doses of 1600 cGy. Thus, at doses of radiation at which IL-12 still protects c-kit+ hematopoietic cells, it sensitizes the intestinal tract to damage. Radioprotection with IL-12 was abrogated by anti-IL-1R or anti-SCF antibody, but not anti-IFN gamma antibody. In contrast, anti-IFN gamma antibody abrogated sensitization of the intestinal tract by IL-12.

IL-12 protects bone marrow from and sensitizes intestinal tract to ionizing radiation.

IL-12, a potent stimulator of hemopoietic progenitor cells, was evaluated as a potential protector against 60Co-gamma radiation-induced lethal hemopoietic syndrome in mice. Administration of IL-12 before lethal irradiation of genetically distinct strains of mice, B6D2F1 and C3H/HeJ, protected a significant fraction of both strains of mice from death. Radioprotection was associated with a fivefold increase in the number of bone marrow cells at 6 days after irradiation. Even at supralethal doses of radiation (1200 cGy), the number of c-kit+ bone marrow cells 3 days after irradiation was twofold greater in IL-12-treated mice than in saline-treated mice. However, mice that received IL-12 and 1200 cGy (B6D2F1) or 900 cGy (C3H/HeJ) died of the gastrointestinal syndrome, as was evident by gross necroscopy and histologic evaluation, within 4 to 6 days after irradiation. Induction of the gastrointestinal syndrome in mice not treated with IL-12 required radiation doses of 1500 cGy or greater in both strains. Thus, at doses of radiation at which IL-12 still protects c-kit+ hemopoietic cells, it sensitizes the intestinal tract to damage. Radioprotection with IL-12 was abrogated by anti-IL-1R or anti-stem cell factor Ab. Anti-IFN-gamma Ab did not affect IL-12-induced hemopoietic radioprotection, but abrogated sensitization of the intestinal tract by IL-12. The sensitizing effect of IL-12 may be related to its ability to prime mice to subsequent inflammatory challenge, as demonstrated by an almost 100-fold increase in circulating TNF and IL-6 levels in normal B6D2F1 mice challenged with IL-12 and LPS. This priming effect of IL-12 also was abrogated by anti-IFN-gamma Ab.

Quantitative study of wound infection in irradiated mice.

Bacterial infection of simple wounds was studied directly and quantitatively in adult mice given 6.5 Gy 60Co. Three days later, when neutropenia was evident, the skin and the medial gluteus muscle of anaesthetized mice were incised. A suspension of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae or Streptococcus pyogenes was inoculated into the wound. Bacteria per mg muscle were enumerated 3, 4 or 7 days later. The geometric means of bacteria per mg were greater in irradiated than in non-irradiated mice. Phagocytic cells were present in the wounded tissue. Hence sublethal ionizing radiation enhanced the susceptibility of mice to infections of wounds by these four bacterial species.

Mycobacterium kansasii in a rhesus monkey.

The incidence of pulmonary disease caused by "atypical" mycobacteria has been increasing gradually in the human population since the 1950s. Mycobacterium kansasii and Mycobacterium intracellulare are the two organisms most responsible for this trend. A rhesus monkey was euthanatized and necropsied after reacting positive to mammalian Old Tuberculin on semi-annual testing. Histopathology demonstrated the presence of small numbers of acid fast organisms in pulmonary lesions. Further microbiological testing identified the causative organism as M. kansasii.