Effect of gold on the immune response of mice

Separate concurrent injection of organic gold compounds and antigen into mice resulted in immunoenhancement that could be measured by direct and indirect plaque-forming cells, rosette-forming cells, and serum antibody assays. Kinetics of the immune response showed variable effects through day 9 of the experiment. Studies with British anti-lewisite, a gold antagonist, showed that the gold must stay in the system 1 day to obtain immunoenhancement.</jats:p

Antiglobulin factors in normal mouse serum reacting with enzyme-digested gamma globulin

The presence of antiglobulin factors in normal mouse serum was studied. Mice were injected with human 0 Rh(+) erythrocytes and the resulting gamma globulins were digested with papain. The reaction was demonstrated by agglutinations of human 0 Rh (+) perythryocytes sensitized with the Fab fragments when treated with normal mouse serum. Studies suggested that there are two factors in mice, a 7S AND A 19S globulin form. Cross-reactivity between strains of mice was demonstrated.</jats:p

Corticosteroid modulation of interleukin-1 hematopoietic effects and toxicity in a murine system

Interleukin-1 (IL-1) has been shown to ameliorate the hematopoietic toxicities of antitumor chemotherapeutic agents in both mice and humans. However, IL-1 toxicity in humans is considerable and is similar to the systemic inflammatory toxicities induced by IL-3, IL-6, and other cytokines with pleiotropic biologic activities, eg, fever, nausea, malaise, and hypotension. We hypothesized that corticosteroids may reduce IL-1 toxicity without reducing IL-1 hematopoietic effects in vivo. C3H/HeJ mice (female, 6 weeks) were treated for 7 days subcutaneously with cortisone acetate (CA), (0.1, 0.25, or 0.5 mg/d/mouse), intraperitoneally with IL-1 (1 or 2 micrograms/d/mouse), or both. As expected, IL-1 increased white blood cell counts, splenic granulocyte-macrophage colony-forming units, and spleen cell number, and protected mice from lethal doses of carboplatin (200 mg/kg; Paraplatin, Bristol Laboratories, Evansville, IN) administered the day after completion of the 7 days of IL-1 administration. CA did not significantly block the hematopoietic effects of IL-1 or the ability of IL-1 to protect mice from the hematopoietic toxicity of carboplatin. IL- 1 administered to mice at 8 micrograms/d/mouse for 5 days induced decreased activity, roughening of hair, diarrhea, pancytopenia, multiple metabolic abnormalities, and death in 60% of mice. IL-1 at the therapeutic doses (0.5 to 2 micrograms/d) was not toxic. CA in a dose- dependent manner blocked all of the above mentioned toxicities when administered 24 hours and 30 minutes before each IL-1 injection. CA also decreased IL-1-induced increase in plasma tumor necrosis factor levels at the time point examined.</jats:p

Corticosteroid modulation of interleukin-1 hematopoietic effects and toxicity in a murine system

Abstract Interleukin-1 (IL-1) has been shown to ameliorate the hematopoietic toxicities of antitumor chemotherapeutic agents in both mice and humans. However, IL-1 toxicity in humans is considerable and is similar to the systemic inflammatory toxicities induced by IL-3, IL-6, and other cytokines with pleiotropic biologic activities, eg, fever, nausea, malaise, and hypotension. We hypothesized that corticosteroids may reduce IL-1 toxicity without reducing IL-1 hematopoietic effects in vivo. C3H/HeJ mice (female, 6 weeks) were treated for 7 days subcutaneously with cortisone acetate (CA), (0.1, 0.25, or 0.5 mg/d/mouse), intraperitoneally with IL-1 (1 or 2 micrograms/d/mouse), or both. As expected, IL-1 increased white blood cell counts, splenic granulocyte-macrophage colony-forming units, and spleen cell number, and protected mice from lethal doses of carboplatin (200 mg/kg; Paraplatin, Bristol Laboratories, Evansville, IN) administered the day after completion of the 7 days of IL-1 administration. CA did not significantly block the hematopoietic effects of IL-1 or the ability of IL-1 to protect mice from the hematopoietic toxicity of carboplatin. IL- 1 administered to mice at 8 micrograms/d/mouse for 5 days induced decreased activity, roughening of hair, diarrhea, pancytopenia, multiple metabolic abnormalities, and death in 60% of mice. IL-1 at the therapeutic doses (0.5 to 2 micrograms/d) was not toxic. CA in a dose- dependent manner blocked all of the above mentioned toxicities when administered 24 hours and 30 minutes before each IL-1 injection. CA also decreased IL-1-induced increase in plasma tumor necrosis factor levels at the time point examined.</jats:p

Corticosteroid alteration of carboplatin-induced hematopoietic toxicity in a murine model

Corticosteroids exhibit extensive hematopoietic effects both in vitro and in vivo. Some of the previously studied effects suggested that corticosteroids may alter hematopoietic toxicity of chemotherapeutic agents. In this study, we examined (1) the optimum dose and schedule of cortisone acetate (CA) to reduce hematopoietic toxicity of carboplatin (CB) and (2) possible mechanisms involved in this protective effect. CA given subcutaneously at 0.5 mg/d per mouse for 7 days before CB reduced CB-induced mortality due to neutropenia from 88% in controls to 14% in CA-treated mice (P &lt; .05). Lower CA doses were not effective. Three days of pretreatment (but not 1 day) was as effective as 7 days. CA given after CB had no effect on mortality. Pharmacokinetic studies of CA at 0.5 mg per mouse demonstrated blood levels of cortisol achievable in patients (peak level, 82 micrograms/dL). CA treatment markedly reduced spleen cell number and colony-forming units- granulocyte/macrophage (CFU-GM) as well as bone marrow CFU-GM. Bone marrow CFU-GM removed from CA-treated mice demonstrated increased resistance to platinum and increased resistance to high specific activity 3H-thymidine. These findings suggest that treatment of mice with CA induces cellular resistance of hematopoietic precursors to platinum and, thus, reduces CB hematotoxicity. CA or other corticosteroids may be useful in reducing clinical toxicity of CB.</jats:p