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

Polymorphonuclear leukocyte (PMN) dysfunction has been reported in human im munodeficiency virus (HIV)-infected patients. Interleukin (IL)-15 is a rece ntly discovered cytokine that potentiates antimicrobial functions of normal PMNs, We evaluated the in vitro effect of IL-15 on chemotaxis and fungicid al activity of PMNs from 9 patients with untreated advanced HIV infection, 8 patients with viral suppression after 52 to 130 weeks of highly active an tiretroviral therapy (HAART), and 12 patients with treatment failure. We al so studied oxidative burst and apoptosis of PMNs in 5 patients with untreat ed advanced HIV infection. Twelve healthy donors were included as controls, Chemotaxis and fungicidal activity of unprimed PMNs was significantly lowe r in patients with untreated HIV infection compared with controls. After in cubation with IL-15, a significant increase in PMN chemotaxis and fungicida l activity was found; moreover, IL-15 induced a significant reduction in th e 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. I L-15 significantly enhanced chemotaxis and fungicidal activity also in pati ents with HAART failure, In conclusion, IL-15 is an important cytokine in t he activation of the functional properties of HIV+ PMNs, by delaying apopto sis and enhancing chemotaxis and fungicidal activity, The potent stimulant effect of IL-15 on PMN function was observed in antiretroviral naive patien ts as well as in individuals who were receiving HAART, including those with treatment failure. (C) 2000 by The American Society of Hematology.