scholarly journals Therapeutic Efficacy of Human Macrophage Colony-Stimulating Factor, Used Alone and in Combination with Antifungal Agents, in Mice with Systemic Candida albicans Infection

2000 ◽  
Vol 44 (1) ◽  
pp. 19-23 ◽  
Author(s):  
Tetsuya Kuhara ◽  
Katsuhisa Uchida ◽  
Hideyo Yamaguchi

ABSTRACT We examined the in vivo activity of human macrophage colony-stimulating factor (hM-CSF) against lethal Candida albicans infection in mice. In C. albicans-infected mice which had been immunosuppressed with cyclophosphamide, treatment with hM-CSF at a daily dose of 8 × 105 units/kg of body weight or greater slightly but significantly prolonged survival. Furthermore, the therapeutic efficacy of amphotericin B (AMPH-B) in infected mice was enhanced by its combined use with hM-CSF, while that of fluconazole (FLCZ) was not. The activities of peritoneal macrophages and neutrophils from mice administered hM-CSF plus AMPH-B in combination for inhibition of hyphal growth of C. albicanscells and intracellular phagocytosis and killing of the cells were greater than those of comparable phagocytic cells from control mice to which hM-CSF plus AMPH-B was not administered. These results suggest that intravenous administration of hM-CSF augments the efficacy of AMPH-B by enhancing the antifungal activities of macrophages and neutrophils. Therefore, it is expected that therapy with the combination AMPH-B and hM-CSF could improve the efficacy of AMPH-B and reduce the therapeutic dose of the antifungal drug that is required.

1998 ◽  
Vol 66 (6) ◽  
pp. 2750-2754 ◽  
Author(s):  
László Maródi ◽  
Christophe Tournay ◽  
Rita Káposzta ◽  
Richard B. Johnston ◽  
Nicole Moguilevsky

ABSTRACT Phagocyte myeloperoxidase (MPO) is believed to be particularly important in defense against candida infection. We reported earlier that monocytes, rich in MPO, killed Candida albicans at a significantly higher rate and extent than did monocyte-derived macrophages, known to lack MPO, and that C. albicans is less resistant to MPO-dependent oxidants than less pathogenic Candida species. We hypothesized, therefore, that the capacity of macrophages to kill C. albicans might be improved in the presence of MPO. In this study, we evaluated the ability of recombinant human MPO (rhMPO) to augment the killing of C. albicans by resident macrophages and macrophages activated by recombinant human granulocyte-macrophage colony-stimulating factor. Addition of rhMPO (concentration range, 0.8 to 6.4 U/ml) to suspensions of resident and activated macrophages and opsonizedC. albicans resulted in concentration-dependent and significant increases in candida killing. This enhancement was particularly pronounced with activated macrophages, whetherC. albicans was opsonized or unopsonized and ingested through the macrophage mannose receptor. rhMPO did not affect the killing of C. albicans by monocytes, nor did it affect phagocytosis of opsonized or unopsonized C. albicans. These results indicate that exogenous rhMPO can augment the candidacidal capacity of both resident and activated macrophages, with a more profound effect on activated cells. We suggest that rhMPO may be effective in the treatment of invasive candidiasis.


Blood ◽  
1990 ◽  
Vol 75 (4) ◽  
pp. 846-850 ◽  
Author(s):  
TR Ulich ◽  
J del Castillo ◽  
LR Watson ◽  
SM Yin ◽  
MB Garnick

Abstract Macrophage colony-stimulating factor (recombinant human M-CSF) given as a single intravenous injection to Lewis rats induces a dose-dependent peripheral monocytosis, neutrophilia, and lymphopenia. The monocytosis peaks at 28 to 32 hours with a seven- to eightfold increase in the number of circulating monocytes and promonocytes. The peripheral monocytosis is accompanied by a slight increase in marrow blasts, promonocytes, and monocytes. A monocytopenia reaching a nadir at 15 minutes precedes the monocytosis, suggesting that M-CSF activates circulating monocytes and causes intravascular margination. The M-CSF- induced neutrophilia and lymphopenia are relatively mild in magnitude, are observed between 2 and 16 hours after injection, and are no longer evident at later time-points. The monocytosis was at least partially inhibited by dexamethasone. M-CSF-induced monocytosis most likely reflects a direct effect of M-CSF on marrow monocyte precursor proliferation, maturation, and release, whereas the neutrophilia and lymphopenia may reflect indirect effects mediated by the known ability of M-CSF to cause the release of other cytokines.


2017 ◽  
Vol 98 (5) ◽  
pp. 517-526 ◽  
Author(s):  
Carmen P. Montano Almendras ◽  
Christian S. Thudium ◽  
Henrik Löfvall ◽  
Ilana Moscatelli ◽  
Axel Schambach ◽  
...  

Blood ◽  
1990 ◽  
Vol 75 (4) ◽  
pp. 846-850
Author(s):  
TR Ulich ◽  
J del Castillo ◽  
LR Watson ◽  
SM Yin ◽  
MB Garnick

Macrophage colony-stimulating factor (recombinant human M-CSF) given as a single intravenous injection to Lewis rats induces a dose-dependent peripheral monocytosis, neutrophilia, and lymphopenia. The monocytosis peaks at 28 to 32 hours with a seven- to eightfold increase in the number of circulating monocytes and promonocytes. The peripheral monocytosis is accompanied by a slight increase in marrow blasts, promonocytes, and monocytes. A monocytopenia reaching a nadir at 15 minutes precedes the monocytosis, suggesting that M-CSF activates circulating monocytes and causes intravascular margination. The M-CSF- induced neutrophilia and lymphopenia are relatively mild in magnitude, are observed between 2 and 16 hours after injection, and are no longer evident at later time-points. The monocytosis was at least partially inhibited by dexamethasone. M-CSF-induced monocytosis most likely reflects a direct effect of M-CSF on marrow monocyte precursor proliferation, maturation, and release, whereas the neutrophilia and lymphopenia may reflect indirect effects mediated by the known ability of M-CSF to cause the release of other cytokines.


1991 ◽  
Vol 77 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Asim Khwaja ◽  
Beryl Johnson ◽  
Ian E. Addison ◽  
Kwee Yong ◽  
Karen Ruthven ◽  
...  

1994 ◽  
Vol 8 (1) ◽  
pp. 42-47 ◽  
Author(s):  
K.L. Yong ◽  
T. McNally ◽  
I.J. Mackie ◽  
H. Cohen ◽  
S.J. Machin ◽  
...  

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