The tumor disappearance reaction: an in vivo effect of a noncytotoxic lymphokine active against tumor cells.

A lymphokine, tumor migration inhibition factor (TMIF), that can inhibit the migration of tumor cells in vitro without cytotoxic effect has been described. TMIF can be produced in vitro or in vivo. In the present study, it is demonstrated that administration of TMIF can lead to a transient decrease in recoverable tumor cells from the peritoneal cavities of otherwise untreated mice. This result, which appears to be due to a direct effect of the mediator, rather than a consequence of inflammatory cell accumulation, is analogous to the effect of macrophage migration inhibition factor (MIF) on macrophages in the well known macrophage disappearance reaction. These findings demonstrate that TMIF can exert an effect in vivo predicted from its in vitro properties, and raise the possibility that this effect can be exploited in an appropriate therapeutic model.

Disposition of intravenous and intraperitoneal cefoxitin during chronic intermittent peritoneal dialysis.

The disposition of intravenous and intraperitoneal administered cefoxitin was evaluated in four males undergoing intermittent peritoneal dialysis. Each patient received 1 g of cefoxitin intravenously prior to an eight-hour dialysis; subsequently, one patient received another 1 g intravenous dose prior to an 18-hour dialysis while each of the other three patients had 100 mg of cefoxitin added to their eight hourly exchanges of dialysis fluid with 2 L per exchange. Serial blood, dialysate, and urine samples were collected and analyzed for cefoxitin by a microbiologic assay. Twenty-four hours after intravenous administration, serum cefoxitin concentrations were greater than 16 micrograms/mL (therapeutic breakpoint) in each patient. Mean cefoxitin dialysate concentrations averaged 7.8 +/- 3.8 micrograms/mL and were greater than 16 micrograms/mL in only 2 of 43 exchanges. After intraperitoneal administration, serum cefoxitin concentrations were highest after the eighth exchange (range 5.6 to 10.6 micrograms/mL). Thus, diffusion of cefoxitin across the placental membrane was not extensive. Dialysis removed only 10% to 20% of the intravenous dose.

The effect of lymphokines on macrophage accumulation and disappearance in the peritoneal cavity.

The intraperitoneal injection of antigen into delayed hypersensitive animals or of preformed lymphokines into unimmunized animals can lead to changes in the distribution and content of inflammatory cells within the peritoneal cavity. If a preexisting macrophage-rich exudate is present, then these challenges will lead to a diminution of the number of macrophages recoverable (macrophage disappearance reaction, MDR). If the peritoneal cavity has been unprepared, then the same stimuli will lead to an increase in the number of macrophages (macrophage appearance reaction, MAR). The existence of opposite effects that can be produced at a given site by the same stimuli provides insights into the multiple interactions involved in biologic reactions mediated by complex mixtures of mediators. Such factors include, in addition to the reaction site itself and the kinds of mediators present, both qualitative and quantitative aspects of the target cell population.

Cellular immunity in Hodgkin's disease.

Defective cell-mediated immunity (CMI) occurs early in the course of Hodgkin's disease (HD) and may persist even two years after successful treatment. This has been confirmed by in vivo and in vitro tests performed on 51 untreated and 52 treated patients of HD. The grading of skin reponse in vivo to dinitrochlorobenzene (DNCB) correlated very well with the in vitro leukocyte migration inhibition (LMI) response against phytohemagglutinin (PHA). An inhibitory influence of HD patients' sera was demonstrated by LMI tests in vitro. The response of peripheral leukocytes from HD patients in the LMI tests could be augmented in vitro by addition of levamisole (an immuno-potentiator) to the culture medium, thus pointing to an intrinsic defect in Lymphocytes. The data indicate that defect at multiple sites in the immune system is responsible for persistent anergy in HD.