Monkey hematological studies

Figure 9 shows that as with monkeys, men made more interferon in response to a given dose of poly(ICLC) than did women. Hematologic studies in M.S. patients showed acute changes in total wbc, as well as in lymphocytes and granulocytes. Within 4 hours after injection, total wbc increased. As with the monkeys at the higher dose, there was a marked decrease in lymphocytes and an increase in polymorphonuclear leukocytes. Figure 10 shows a typical reaction. 

Hematological effects were not reported in monkeys, rats, or mice exposed to 5 ppm phenol in air for 90 days (Sandage 1961), or in rats exposed to 26 ppm continuously for 15 days (Dalin and Kristoffersson 1974). Studies in which the ratio of polychromatic to normochromatic red blood cells in the bone marrow of mice treated with one (Barale et al. 1990) or three (Chen and Eastmond 1995a) intraperitoneal injections of phenol did not show an adverse effect. 

Studies in rats suggested that cyanogen is 10-fold less acutely toxic than hydrogen cyanide. In rats and monkeys exposed to 11 or 25 ppm cyanogen for 6 hours/day, 5 days/week for 6 months, there were no effects on hematologic or clinical chemistry values. Mean body weights were reduced in rats at the higher level. 

No adverse effects were reported for a large number of hematological parameters in rats or monkeys exposed to 1 ppm hydrazine continuously for 6 months (Haun and Kinkead 1973). In dogs, the anemic effects of hydrazine in this study and 1,1-dimethylhydrazine in the Rinehart et al. (1960) study appear to be fairly similar, and the data suggest that dogs may be particularly sensitive to the hematological effects... 

In the rabbit brain safety study using P(CPP-SA) 50 50 copolymer, even less of an inflammatory reaction was observed, and the polymer was essentially equivalent to Gelfoam [94]. In a similar brain biocompatibility study conducted in monkeys, no abnormalities were noted in the computer tomography scans and magnetic resonance images, nor in the blood chemistry or hematology evaluations [95]. No systemic effects of the implants were observed on histological examinations of any of the tissues tested [96]. No unexpected or untoward reactions to the treatments were observed. 

Yoshida, T., K. Ohtoh, H. Narita, F. Ohkubo, F. Cho, andY. Yoshikawa. 1994. Feeding experiment on laboratory-bred male cynomolgus monkeys. II. Hematological and serum biochemical studies. Experimental Animals 43 199-207. 

Hematology tests and serum chemistries for all treated monkeys were normal and viremia (relative to the controls) was minimal even at the low dose of 3 mg/kg/day. While the control monkeys developed severe rash, none of the FEAU-treated monkeys developed rash at these drug levels. Further studies showed that a lower dose of 1 mg/kg/day prevented development of rash but did not reduce viremia in two out of three monkeys. These data suggest that the minimal effective dose in this system for FEAU is 1 mg/kg/day. Concurrent studies with FMAU showed it to be 40-fold more potent against SVV with a minimal effective dose of 0.04 mg/kg/day x 10. 

All the material presented so far has been a review of previously published work. The second part of this presentation deals with unpublished studies on hematological and cell associated immune modifications induced in monkeys and people by poly(ICLC). Table 9 lists the names of people who contributed to the work to be reported. 

First, the data obtained in studies with monkeys will be given. Poly-(ICLC) was injected, i.v., into 2 monkeys at two different dose levels according to the following protocol. On day 0 blood was drawn for the determination of several hematological and immunological parameters. The first injection of poly(ICLC) was then given, i.v., at 0.2 mg/m. Then, 24 hours later (day 1) blood was drawn for the same battery of tests, and... 

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