Immune reconstitution: is there a potential role for Filgrastim (r-metHuG-CSF).

Abstract

U C C E SS O F IM M U N E RE CO N ST IT U T IO N depends upon success of hematopoietic reconstitution as a first step, and hematopoietic reconstitution, in turn, depends on the subtle actions and interactions of various hematopoietic cytokines and growth factors. Hematopoietic growth factors and cytokines may be particularly important modulators of immune reconstitution because they can increase the number of leukocytes, recruit immature leukocytes, cause maturation and augmentation of leukocytes, and suppress leukocytes. As optimism for immune reconstitution in the setting of HIV infection increases, a careful review of the potential role of growth factors in this process is warranted. Filgrastim (r-metHuG-CSF) is a hematopoietic growth factor that selectively allows the proliferation, differentiation, and maturation of neutrophil precursors. It is known to increase the number of neutrophils (leukocytes) rapidly (1) and can recruit immature cells from the bone marrow (1). Filgrastrim also is known to modulate neutrophil functions (2‐ 6). Replication of HIV appears to be an active and continuous process, with progressive hematopoietic destruction as a result. The resulting immunodeficiency caused by HIV combines active destruction of CD4 1 cells, impairment of regeneration of CD4 1 cells and other hematopoietic cells, and impairment of the immune system. Because HIV can mutate, it is not clear how destruction and impairment change over time, and which, if any of the processes, is most important. Patients with HIV disease have major defects of the immune signaling system, specifically in the cytokinemediator system (7), and an increase in proinflammatory cytokines (8,9). Increases in some proinflammatory cytokines, such as tumor necrosis factor and interferon- g are thought to promote viral replication. Lymphokines, such as IL-2, may facilitate the progression from HIV infection to AIDS, because IL-2 formation by CD4 T cells appears to be required to maintain CD8 T cell control of viral replication (10). Studies have suggested clinical benefit from administration of rHuIL-2 to HIV-infected patients (11). A recent study has shown that Filgrastim can restore IL-2 production in blood of HIV-infected patients (12).