Effect Of In vivo Infusion of Granulocyte Colony-Stimulating Factor on Immune Function

Abstract

As the applications of hematopoietic growth factors increase, their complex impact on host defense and immune responses continues to unfold. The effect of the administration of granulocyte colony-stimulating factor (G-CSF) on bacterial defense, proliferation of lymphocytes, and cytokine production by lymphocytes and peripheral blood mononuclear cells (PBMC) was studied. The effect of G-CSF administration on the phenotype of the cells in the major hematopoietic organs was studied as well. ACI rats were given 10 mg/kg/day G-CSF or vehicle daily for 4 days. Isolated bone marrow neutrophils and enterocytes from treated animals showed a greater bactericidal activity than controls. Proliferation of mitogen-stimulated lymphocytes and PBMC was reduced in G-CSF-treated animals. The production of proinflammatory cytokines, tumor necrosis factor (TNF), and interleukin 6 (IL-6) by lymphocytes and PBMC was reduced by G-CSF pretreatment. G-CSF administration caused an increase in IL-4 (Th2 cytokine) release and a decrease in interferon-gamma (IFNgamma, Th1 cytokine) release by mitogen-stimulated lymphocytes. Cytometric analysis of cells in the progenitor cell region indicated a large increase in immature cells in the bone marrow of G-CSF-treated animals compared with sham along with an increase in B cells and a decrease in polymorphonuclear leukocytes (PMNs). In addition, cytometric analysis showed a large increase in PMNs in blood and splenocytes of the treated animals compared with sham. This study confirms and extends previous observations that G-CSF administration has a number of effects that might simultaneously enhance host defense while reducing the risk of developing uncontrolled systemic inflammation. This may also be efficacious in prolonging graft survival and reducing graft vs. host disease.

Mechanism of salutary effects of estradiol on organ function after trauma-hemorrhage: upregulation of heme oxygenase

“…Thus the salutary effects of estradiol administration on organ function after trauma-hemorrhage are mediated in part via upregulation of HO-1 expression and activity. hemorrhagic shock; heme oxygenase-1; chromium mesoporphyrin; liver; heart IT IS WELL ESTABLISHED THAT shock decreases organ perfusion and depresses organ as well as immune functions (2,9,12,32,38,42). There is also a growing body of evidence that indicates that heme degradation products [i.e., carbon monoxide (CO), biliverdin, bilirubin] may counteract the detrimental consequences of decreased organ perfusion and ischemia-reperfusion-related injury (1, 27) following low-flow conditions.…”

Mirimostim (macrophage colony‐stimulating factor; M‐CSF) improves chemotherapy‐induced impaired natural killer cell activity, Th1/Th2 balance, and granulocyte function

“…As a rule, chemotherapy was administered every 3 weeks. After the completion of one course of chemotherapy, the next course of chemotherapy was administered after confirmation of the recovery of the white blood R 5 To whom correspondence should be addressed. E-mail: s30saito@ms.toyama-mpu.ac.jp cell, granulocyte, and platelet counts to 3000/mm 3 or greater, 1500/mm 3 or greater, and 10×10 4 /mm 3 or greater, respectively.…”

“…Recent studies have shown that CSFs not only increase granulocyte counts, but also modify immunological functions: G-CSF decreases the natural killer (NK) cell count in the peripheral blood mononuclear cells (PBMCs) 1) and NK cell activity, 2,3) and drives T cell polarization toward a T-helper cell 2 (Th2) phenotype. [4][5][6][7][8][9] Whereas these actions decrease graft-versus-host disease (GVHD) associated with hematopoietic stem cell transplantation, they may worsen the long-term prognosis of leukemia by lessening the graft-versus-leukemia (GVL) effect. GM-CSF has been reported to inhibit the decrease in NK and lymphokine-activated killer (LAK) activity caused by chemotherapy for solid cancers.…”

Lymphocyte subpopulation and dendritic cell phenotyping during antineoplastic therapy in human solid tumors

“…Hematological support with granulocyte-colonystimulating factor (G-CSF), either natural or pegylated, was demonstrated to reduce the duration and severity of CTinduced neutropenia and thus infectious complications and hospitalizations. G-CSF also has an impact on the immune system; it has been shown to influence cytokine production and to modify T-and B-lymphocyte subsets [49][50][51].…”