Normalization of anti-cryptococcal activity and interleukin-12 production after highly active antiretroviral therapy.
OBJECTIVE
To investigate the effect of highly active antiretroviral treatment (HAART) on antifungal and secretory functions of polymorphonuclear leukocytes (PMNL) from HIV-infected patients with high viral load.


METHODS
Antifungal activity, oxygen-dependent mechanisms and interleukin (IL)-12 secretion were evaluated in PMNL from HIV-infected patients before and 3 months after commencing HAART.


METHODS
PMNL antifungal activity was evaluated by effects on fungal colony-forming units. Superoxide anion (O2-) production was determined by superoxide dismutase reduction and IL-12 was determined by enzyme-linked immunosorbent assay in supernatant fluids of PMNL cultured for 18 h.


RESULTS
PMNL from HIV-infected patients showed dysregulation of antimicrobial and secretory functions. A selective defect in antimicrobial activity against encapsulated Cryptococcus neoformans correlated with baseline O2- overproduction, which drastically decreased upon microbial stimulation. Similarly, constitutive secretion of IL-12 was blocked by exposure to microbial products. PMNL analysed after 3 months of HAART showed restoration of antimicrobial activity against encapsulated C. neoformans, reduction in O2- formation by unstimulated cells and restoration of oxidative burst after appropriate stimulation, and reduction of IL-12 hypersecretion.


CONCLUSIONS
PMNL from HIV-infected patients with high viral load have impaired function; HAART normalizes antimicrobial and secretory activities. The effects of HAART on innate immunity provide new prospects for reduction of HAART-mediated opportunistic infections.
Monari
C
C
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Casadevall
A
A
Baldelli
F
F
Francisci
D
D
Pietrella
D
D
Bistoni
F
F
Vecchiarelli
A
A
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002175:Candida / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D013481:Superoxides / Q000378:metabolism; D019562:Viral Load
D019380:Anti-HIV Agents; D012367:RNA, Viral; D013481:Superoxides; D018664:Interleukin-12