In a recent study involving normal, juvenile mice, we showed that CVT-E002, a proprietary extract (Afexa Life Sciences, Inc.) of North American ginseng, Panax quinquefolius, significantly enhanced the absolute levels of cells acting at the first line of defense in tumor combat, i.e., natural killer (NK) cells. The present study evaluated the effect of CVT-E002, on life span when administered intraperitoneally to leukemic, infant/juvenile mice. The extract was administered to groups of mice daily for 14 days in several dosing groups up to 50mg/day from age 7 to 21 days. The tumor was administered intraperitoneally under sterile conditions, in a laminar flow hood at 7 days of age (0.5 x 10(6) leukemic cells), immediately preceding the first CVT-E002 injection for each dose group. The data revealed that CVT-E002 significantly extends the life of leukemic, young mice in a dose-specific manner, i.e., 20 mg/day was effective in extending life, while lower doses of 5, 10 mg as well as higher doses of 30, 40, 50 mg per day were completely ineffective. We have already shown that CVT-E002 significantly elevates NK cells in normal and leukemic, adult mice, as well as in normal, infant/juvenile mice, and we have also shown that CVT-E002 significantly extends the life span of leukemic, adult mice. The results of the present study did indeed show that (i) CVT-E002 extends the life span of leukemic, infant/juvenile mice, and (ii) that the dose of CVT-E002 is critical in achieving life span augmentation in these leukemic infant/juvenile mice.
The present study evaluated the effect of CVT E002, a proprietary extract of North American ginseng, Panax quinquefolius (CV Technologies, Inc., Edmonton, AB, Canada), in vivo, on the hemopoietic and immune cells when administered intraperitoneally to infant (pre-weaned) mice. The extract was administered to groups of mice daily, for 14 days, from 7 21 days after birth, the dosage being adjusted progressively according to body weight as the infants grew. At 21-26 days of age, the period immediately after the last of the injection, and at 7-8 weeks of age, long after the termination of CVT E002, the bone marrow and spleen were removed from treated and control mice (CVT E002-injected and vehicle-injected, respectively). The results revealed that CVT E002 stimulated only those cells acting as the first line of defense against cancer, i.e., natural killer (NK) cells and granulocytes when assessed immediately after termination of CVT E002. However, even more potentially significant, was the observation that in spite of withdrawing the agent at weaning (21 days of age), the influence of CVT E002 had indirectly continued to produce a significant augmentation in NK cells and granulocytes in adulthood. Thus, CVT E002 may be considered as a dietary additive, fortifying anti-cancer immunity during the critical infant/juvenile ages when, in humans at least, pediatric cancers such as leukemia, lymphomas, Wilms tumors and retinoblastoma are relatively frequent.
Epidemiological studies indicate that the incidence of Type 1 diabetes, an autoimmune disease, is rising rapidly. However, none of the current therapies produces life long remission, or can prevent the disease onset. The NOD (non-obese diabetic) mouse is currently regarded as an excellent animal model of human Type 1 diabetes. NKT cells are known to be fundamental in modulating the disease, yet they are numerically and functionally deficient in mammals bearing this disease. Indeed, the role of NK cells in inhibiting autoimmunity in general is well established. Immunoregulatory strategies are currently believed to be the way of the future with respect to modulating autoimmune diseases. Based on this hypothesis, and the fact that the herb, Echinacea, is a well demonstrated immunostimulant of NK cells in normal mice/humans, we aimed to investigate, in NOD mice, the effect of short term (days) and long term (months) daily dietary administration of Echinacea, on the absolute levels of NK cells, and five other classes of hemopoietic and immune cells, in the bone marrow and spleen. The results revealed that, in NOD mice, dietary Echinacea, resulted in a significant increase in the absolute numbers of NK cells, irrespective of feeding duration, in the spleen, and moreover, it actually stimulated NK cell production in their bone marrow birth site. We further found that there were transient, early (days), herb exposure-time-dependent, quantitative changes in several of the other hemopoietic and immune cells populations in both the bone marrow and spleen. We conclude that consumption of this herb by NOD mice, at least, has lead to no negative repercussions with respect to the hemopoietic and immune lineages, and secondly, the consistent, long-lasting immunostimulation only of NK cells, may lead to a possible new approach to the treatment of Type 1 diabetes.
The normal regulation of primitive hemopoietic stem cells (PHSCS) throughout development involves locally produced factors and humoral factors. While considerable information is available on the effects of candidate hemopoietic growth factors (HGFs) on postnatal hemopoietic tissues, little is known about the regulatory events of developing hemopoietic stem cells within fetal microenvironments. Fetal hemopoiesis represents expanding populations and may be under different regulatory control mechanisms. The microinjection of purified interleukin-3 (IL-3), a candidate HGF, into 13-day-old mouse fetuses via the yolk sac, allowed us to evaluate its effects on morphogenetic events and, more specifically, on fetal liver populations using quantitative in vitro clonal assays for hemopoietic precursors. In view of the sensitivity of fetal development during the early organogenetic period, considerable care was taken to identify the stress effects of the surgical laparotomy and the microinjection procedure. Control studies, required to distinguish stress effects of surgical laparotomy and microinjection, clearly revealed that the fetal liver is a sensitive organ responding with limited tissue disorganization, reduced cellularity and erythropoietic activity, as monitored 24 h after experimental intervention. The microinjection of 15 units of IL-3 promoted a significant expansion of depleted liver hemopoietic-cell populations and had stimulatory effects on the distribution of connective tissue mast cells and absolute cell numbers, including hemopoietic precursors (erythroid, granulocyte, macrophage, megakaryocyte), compared to controls. These studies suggest that (1) fetal liver hemopoiesis is selectively sensitive to maternal stress but has an effective regenerative capacity to maintain essential hemopoiesis in utero, and (2) fetal hemopoietic cells acquire an ability to respond to IL-3 early in fetal development.
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