C. Monari et al., Normalization of anti-cryptococcal activity and interleukin-12 production after highly active antiretroviral therapy, AIDS, 14(17), 2000, pp. 2699-2708
Objective: To investigate the effect of highly active antiretroviral treatm
ent (HAART) on antifungal and secretory functions of polymorphonuclear leuk
ocytes (PMNL) from HIV-infected patients with high viral load.
Design: Antifungal activity, oxygen-dependent mechanisms and interleukin (I
L)-12 secretion were evaluated in PMNL from HIV-infected patients before an
d 3 months after commencing HAART.
Methods: PMNL antifungal activity was evaluated by effects on fungal colony
-forming units. Superoxide anion (O-2(-)) production was determined by supe
roxide dismutase reduction and IL-12 was determined by enzyme-linked immuno
sorbent assay in supernatant fluids of PMNL cultured for 18 h.
Results: PMNL from HIV-infected patients showed dysregulation of antimicrob
ial and secretory functions. A selective defect in antimicrobial activity a
gainst encapsulated Cryptococcus neoformans correlated with baseline O-2(-)
overproduction, which drastically decreased upon microbial stimulation. Si
milarly, constitutive secretion of IL-12 was blocked by exposure to microbi
al products. PMNL analysed after 3 months of HAART showed restoration of an
timicrobial activity against encapsulated C. neoformans, reduction in O(2)(
-)formation by unstimulated cells and restoration of oxidative burst after
appropriate stimulation, and reduction of IL-l;! hypersecretion.
Conclusions PMNL from HIV-infected patients with high viral load have impai
red function; HAART normalizes antimicrobial and secretory activities. The
effects of HAART on innate immunity provide new prospects for reduction of
HAART-mediated opportunistic infections. (C) 2000 Lippincott Williams & Wil
kins.