Repetitive intraperitoneal sublethal doses of human tumor necrosis factor alpha (TNF) protect rats against the lethality, hypotension and hypothermia of gram negative sepsis induced by cecal ligation and puncture. The protective effects of TNF is associated with induction of the gene for manganous superoxide dismutase (MnSOD). Similarly, a single iv dose of either interleukin-1(IL-1) or TNF produces similar protection through a similar mechanism. Moreover, a specific receptor antagonist to IL-1 protects mice against the lethality of endotoxin (LPS) when given iv 1/2h following a lethal dose of endotoxin. This finding implies that IL-1 (in addition to TNF) is responsible for the lethality of LPS and that the IL-1 receptor antagonist may be a new treatment strategy to reverse lethal endotoxemia. Furthermore, interferon-gamma may also be responsible for the lethality of LPS and the cachexia of cancer. Specific antibodies to it reverse the lethality of LPS when administered 6h before LPS and the late cachectic decline of tumor-bearing rate resulting in prolonged survival. Pentoxifyline inhibits TNF secretion by macrophages both in vitro and in vivo. It inhibits secretion at the level of TNF gene transcription. It may have promise in conditions that are mediated through excessive TNF secretion. Since 1980, 73 patients who presented with localized disease had surgery to resect all gastrinoma as part of a prospective strategy to manage patients with Zollinger-Ellison syndrome (ZES). The immediate cure-rate was 58% and the long-term (5-year) cure rate was 38%. Of the patients who presented with liver metastatic disease, the 5 year survival was 20%. This study suggests that there are 2 groups of patients with ZES: localized disease, the majority of patients who can be cured, and distant disease, approx 1/4 of patients who need more aggressive anti-tumor treatment.
