We report downregulatory effects of granulocyte colony-stimulating factor (G-CSF) on allogeneic immune responses in vitro. G-CSF did not affect the proliferative response of peripheral blood mononuclear cells (PBMC) against allogeneic Daudi cells but did inhibit tumor necrosis factor (TNF)-alpha secretion. In contrast with G-CSF, granulocyte- macrophage (GM)-CSF and interleukin (IL)-3 enhanced alloactivation- induced TNF-alpha production. G-CSF-mediated suppression of TNF-alpha production was not affected by fixation of stimulators. G-CSF did not inhibit TNF-alpha mRNA expression or accelerate mRNA degradation, whereas pentoxifylline inhibited the expression of TNF-alpha mRNA. These results indicate that G-CSF acts directly on responder cells and modulates TNF-alpha production at posttranscriptional levels. Suppression of TNF-alpha secretion was accompanied by an increase of intracellular cyclic adenosine monophosphate (cAMP) concentration in alloactivated PBMC. The cell-permeable cAMP analogue, dibutyryl cAMP, suppressed TNF-alpha secretion without affecting TNF-alpha mRNA expression. G-CSF showed an inhibitory effect on the development of cytotoxic effector cells against allogeneic Daudi cells. Anti-TNF-alpha monoclonal antibody (MoAb) also inhibited the induction of cytolytic activity, and the inhibitory effects of G-CSF and anti-TNF-alpha MoAb on killer activity generation were overcome by adding exogenous TNF- alpha. Hence, impaired generation of cytolytic effector cells by G-CSF is believed to be the result of reduced TNF-alpha production. Collectively, the results described above suggest that G-CSF downregulates allogeneic immune responses by posttranscriptionally inhibiting TNF-alpha production.
We describe a 68-year-old Japanese male with hypoplastic acute myelogenous leukemia (AML) who achieved complete hematological reconstitution following granulocyte colonystimulating factor (G-CSF) administration. The patient had pancytopenia and the bone marrow was hypocellular with 19 to 36%peroxidase-positive blasts without morphological abnormalities suggestive of myelodysplasia. After receiving G-CSFas a supportive therapy for pneumonia, the blood count became normal and the bone marrowwas normocellular with less than 5%of blasts. Without subsequent chemotherapy, he relapsed as a form of overt leukemia and died of pneumonia. Chemotherapy may be necessary to maintain remission in hypoplastic AMLafter hematopoietic reconstitution by G-CSF. (Internal Medicine 34: 692-694, 1995)
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We describe a 74-year-old patient with multicentric Castleman's disease (MCD) whose serum macrophage colony-stimulating factor level was elevated. Serum levels of tumor necrosis factor-alpha and interleukin 6 were also elevated at presentation, and they returned to normal levels after chemotherapy. Although the total serum cholesterol level was below normal on admission, it increased after chemotherapy. These results suggest that the activation of monocytes or macrophages may be involved in certain pathological phenomena in MCD.
We investigated the mechanism of polyclonal B cell differentiation in mantle cell lymphoma (MCL) using peripheral blood mononuclear cells (PBMC) from a patient with MCL in leukemic stage presenting polyclonal hypergammaglobulinemia. Patient T cells not only responded to autologous non-T cells but induced polyclonal production of IgG in vitro. Flow cytometric analysis of PBMC showed the increased conversion of CD4+ T cells from the naive to the memory state. We propose the possible mechanism that autoreactive T cells may be involved in polyclonal B cell differentiation in this monoclonal B cell disorder.
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