Filgrastim Restores Interleukin‐2 Production in Blood from Patients with Advanced Human Immunodeficiency Virus Infection

Abstract

and Albrecht WendelFilgrastim induces lymphocytosis, including all T cell subsets, and increased ex vivo interleukin (IL)-2 release as well as lymphocyte proliferation. Since Filgrastim is increasingly used in patients with human immunodeficiency virus (HIV) infection, the effect of Filgrastim on ex vivo cytokine production was determined. Whole blood from 8 healthy volunteers, 5 high-risk volunteers, and 31 HIV-infected outpatients was assayed for cytokine production in response to endotoxin (LPS) or staphylococcal enterotoxin B (SEB) in the presence or absence of 100 ng/mL Filgrastim. LPSinducible blood cytokine release of HIV-infected patients was not different from that of normal or high-risk volunteers. The suppressive effect of Filgrastim on LPS-inducible blood tumor necrosis factor-a and interferon-g formation in normal volunteers was not found in HIV-infected patients. Patients with advanced HIV infection showed reduced IL-2 and IL-4 release in the presence of SEB. In the presence of Filgrastim, IL-2 production was partially restored.Filgrastim (granulocyte colony-stimulating factor, r-metHuG-HIV-infected patients are known to develop major defects of the immune signaling system [20], in particular of the cytokine-CSF) is a hematopoietic growth factor primarily of neutrophilic granulocytes. It is used clinically to treat neutropenia due to mediator system. Some proinflammatory cytokines, such as tumor necrosis factor (TNF)-a and interferon (IFN)-g, are myelosuppressive chemo-or radiation therapy, severe chronic neutropenia, human immunodeficiency virus (HIV) infection, and found to be increased [5, 21 -23] and have been implicated in the promotion of viral replication [24]. More recently, lymphoother diseases [1]. HIV-infected patients may develop neutropenia because of the myelosuppressive effects of HIV or because kines, such as interleukin (IL)-2, have been thought to play an important role in the progression of HIV infection to AIDS. of some of the drugs used to treat these patients [2]. Both HIVinfected patients and HIV-infected leukocytes have shown a re-IL-2 formation by CD4 T cells appears to be mandatory in maintaining CD8 T cell control of viral replication [25]. A duced ability to produce G-CSF [3][4][5]. Neutropenia appears to be a risk factor and contributes to the increased incidence of switch from Th1-type lymphokines (primarily IL-2) to Th2-type lymphokines (IL-4, IL-10) was suggested to represent the infections in neutropenic HIV-infected patients [6][7][8], and Filgrastim treatment has been shown to reverse neutropenia in HIVchange from asymptomatic HIV infection to AIDS [26]. Studies have shown that G-CSF has a widespread effect as infected patients and to decrease infection [9][10][11][12][13][14]. A number of functional defects of neutrophils have been reported for HIVan immunomodulator controlling the functions and activity of mature neutrophilic granulocytes [27, 28] and has profound infected patients [15][16][17] that could be reversed by Filgrastim antiinflammatory effects on m...

Granulocyte Colony‐Stimulating Factor Increases CD4+T Cell Counts of Human Immunodeficiency Virus–Infected Patients Receiving Stable, Highly Active Antiretroviral Therapy: Results from a Randomized, Placebo‐Controlled Trial

“…The recombinant form of granulocyte colony-stimulating factor (G-CSF), a hematopoietic growth factor that acts specifically on neutrophil precursors and mature neutrophils to enhance their functions, is used to treat neutropenia resulting from myelosuppressive chemotherapy or radiation therapy, severe chronic neutropenia, and other neutropenic and nonneutropenic conditions (reviewed in [5]). Studies of short-term treatment with G-CSF of patients infected with HIV have demonstrated increases in CD4 ϩ cell count [6] and partial restoration of interleukin-2 (IL-2) production in vitro [7]. Use of recombinant G-CSF also increases neutrophil counts and decreases bacterial infections in HIV-infected patients with neutropenia [8,9].…”

“…Hartung et al [7] found that G-CSF (filgrastim) in vitro partially restored IL-2 production. In the present study, we were not able to confirm this.…”

Increased Replication of HIV‐1 Minor Variants during Hematopoietic Stem‐Cell Mobilization with Filgrastim

“…G-CSF also modulates cytokine production directly in monocytes and either directly or indirectly in lymphocytes [23][24][25][26][27]. Last, filgrastim partially restores defective IL-2 release from the blood cells of HIV-1-infected persons [28]. Thus, there are several plausible mechanisms by which filgrastim treatment could stimulate HIV-1 replication.…”

Modulation of Cytokine Release in Ex Vivo-Stimulated Blood from Borreliosis Patients

“…The cytokine release capacity of blood from patients and healthy controls can be used for comparative studies, and alterations have been detected in blood from patients with multiple sclerosis (6), malignant melanoma (7), rheumatoid arthritis (14), multiple myeloma (26), and human immunodeficiency virus infection (17) and children infected with enterohemorrhagic E. coli (38). Particularly because leukocyte counts are not affected in Borrelia infection (34, 37), it seemed appropriate to take a similar approach to characterize possible changes of the immune response in patients with persistent Borrelia infection.…”