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Interleukin-15 enhances neutrophil functional activity in patients with human immunodeficiency virus infection
C M Mastroianni1, G d'Ettorre, G Forcina
1Department of Infectious and Tropical Diseases, La Sapienza University, Rome, Italy. cm.mastroianni@tiscalinet.it
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. (Blood. 2000;96:1979-1984)
Insights
Interleukin-15 (IL-15) enhances polymorphonuclear leukocyte (PMN) function in patients with human immunodeficiency virus (HIV). This cytokine improves PMN chemotaxis and killing activity, while reducing apoptosis, benefiting both untreated and treated HIV patients.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Polymorphonuclear leukocyte (PMN) dysfunction is a known complication in human immunodeficiency virus (HIV) infection.
- Interleukin-15 (IL-15), a cytokine, is recognized for its ability to enhance the antimicrobial functions of normal PMNs.
Purpose of the Study:
- To investigate the in vitro effects of IL-15 on the chemotaxis and fungicidal activity of PMNs from HIV-infected patients.
- To assess the impact of IL-15 on oxidative burst and apoptosis in PMNs from individuals with untreated advanced HIV infection.
Main Methods:
- Evaluated PMN chemotaxis and fungicidal activity in vitro.
- Studied oxidative burst and apoptosis of PMNs.
- Compared PMN function in untreated HIV patients, HAART-treated patients (viral suppression and treatment failure), and healthy controls.
Main Results:
- PMNs from untreated HIV patients showed significantly lower chemotaxis and fungicidal activity compared to controls.
- IL-15 significantly increased PMN chemotaxis and fungicidal activity, and reduced apoptosis in HIV-infected individuals.
- IL-15 fully restored defective PMN function in long-term HAART-suppressed patients and enhanced function in those with HAART failure.
Conclusions:
- IL-15 is crucial for activating functional properties of HIV-infected PMNs by delaying apoptosis and enhancing chemotaxis and fungicidal activity.
- The potent stimulatory effect of IL-15 on PMN function is evident in both antiretroviral-naive and HAART-treated HIV patients, including those with treatment failure.