Interleukin-15 enhances neutrophil functional activity in patients with human immunodeficiency virus infection

Abstract

Polymorphonuclear leukocyte (PMN) dysfunction has been reported in human immunodeficiency virus (HIV)-infected patients. Interleukin (IL)-15 is a recently discovered cytokine that potentiates antimicrobial functions of normal PMNs. We evaluated the in vitro effect of IL-15 on chemotaxis and fungicidal activity of PMNs from 9 patients with untreated advanced HIV infection, 8 patients with viral suppression after 52 to 130 weeks of highly active antiretroviral therapy (HAART), and 12 patients with treatment failure. We also studied oxidative burst and apoptosis of PMNs in 5 patients with untreated advanced HIV infection. Twelve healthy donors were included as controls. Chemotaxis and fungicidal activity of unprimed PMNs was significantly lower in patients with untreated HIV infection compared with controls. After incubation with IL-15, a significant increase in PMN chemotaxis and fungicidal activity was found; moreover, IL-15 induced a significant reduction in the number of apoptotic HIV+ PMNs. IL-15 did not modulate oxidative burst of HIV+ PMNs as measured by chemiluminescence production. The in vitro priming of PMNs with IL-15 determined a complete reversal of defective chemotaxis and killing in all HAART-treated patients with long-term HIV suppression. IL-15 significantly enhanced chemotaxis and fungicidal activity also in patients with HAART failure. In conclusion, IL-15 is an important cytokine in the activation of the functional properties of HIV+ PMNs, by delaying apoptosis and enhancing chemotaxis and fungicidal activity. The potent stimulant effect of IL-15 on PMN function was observed in antiretroviral naive patients as well as in individuals who were receiving HAART, including those with treatment failure.

Immune activation in the course of HIV‐1 infection: Causes, phenotypes and persistence under therapy

“…In the same vein, ROS are spontaneously produced by circulating neutrophils , and this might explain why, according to some authors but not others , they are poorly reactive under stimulation. An exacerbated susceptibility to apoptosis in the absence of stimuli has also been reported and it is interesting to note that the phagocytosis of apoptotic neutrophils by macrophages is an additional source of inflammation . Neutropenia may occur at late stages of the disease.…”

“…Neutropenia may occur at late stages of the disease. An impairment in the response to chemo attractants has also been reported , which is incompletely restored under HAART . In contrast, the capacity of neutrophils from infected patients to produce inflammatory cytokines under exposure to LPS or Candida is exaggerated .…”

Interleukin-15 production by monocyte-derived dendritic cells and T cell proliferation in HIV-infected patients with discordant response to highly active antiretroviral therapy

“…In addition, IL‐15 is able to stimulate functional properties of neutrophils from HIV‐infected patients. Alterations of the production of IL‐15 by peripheral blood mononuclear cells (PBMC) from HIV‐infected patients has been observed recently [13,17,18]. Furthermore, IL‐15 is able to stimulate HIV‐positive monocytes to produce important chemokines such as IL‐8 and monocyte chemoattractive protein (MCP)‐1, and has no major effect on HIV replication in vitro [19].…”

Granulocyte macrophage colony stimulating factor

“…Indeed, neutrophil dysfunction and neutropenia were identified as clinical signs of HIV/AIDS before the HIV virus had been identified (62). These defects in neutrophil function result in increased susceptibility to bacterial and fungal infections, and are likely a major contributor to the increased morbidity/mortality seen in HIV patients (63)(64)(65)(66). Highly active antiretroviral therapy can effectively control HIV infection.…”