376 Enhancement of Natural Killer Cell Number and Cytokine-driven Activation in HIV-1+ Patients Recieving Growth Hormone and HAART M. Goodier*1, N. Imami1, G. Moyle2, L. Rennalls1, B. Gazzard2, F. Gotch1 1Imperial Coll Faculty of Med, Chelsea and Westminster Hosp, London, UK and 2Chelsea and Westminster Hosp, London, UK
Background: Natural Killer (NK) cells are reduced in number, have altered surface expression of inhibitory receptors (CD94-NKG2A), and have impaired functional capacity during chronic untreated HIV infection. As observed for CD4+ T-cells, NK cell numbers are recovered, at least in part, during highly active anti-retroviral therapy (HAART). However, recent studies suggest that despite this recovery in cell number, the NK cell pool remains functionally impaired. Immuno-therapeutic strategies for chronic HIV-1 infection have sought to enhance virus-specific immunity within the CD4 and CD8 T-cell compartments. Recently, we have shown that concomitant administration of recombinant human growth hormone (rhGH) with HAART results in the transient re-emergence of virus-specific CD4 and CD8 T-cell responses as determined by IFN-gamma production and lympho-proliferation.
Methods: We assessed whether NK cell function would be similarly affected by rhGH therapy during HAART. Twelve (12) HIV-1 infected individuals with lipodystrophy on long-term successful HAART received rhGH. NK cell numbers and phenotype were monitored in these individuals before and after rhGH therapy. The effect of rhGH therapy on IL-2 + IL-12 or IL-15 + IL-12 driven NK activation IFN-gamma production was then monitored in individual patients (pts) and compared to normal controls.
Results: Increases over baseline values in absolute numbers and percentages of NK cells were observed by wk 12 of treatment in 7 out of 12 pts receiving GH and HAART. No significant changes in the distribution of Killer Ig-like receptors or CD94-NKG2A were observed in such individuals on growth hormone treatment. However, increases in NK cell CD69 expression in response to IL-2 (baseline (b) = 47.3 ±28.4%; GH=71.4 ±23.8%) and, to a lesser extent, IL-15 (b = 68.2 ±25.0; GH = 82.9 ±13.4%) were observed. Such increases were reflected in IFN-gamma production: IL-2 (b = 2.4 +±2.1%, GH = 5.0 ±2.9%); IL-15 (b = 4.7 ±3.4%, GH = 6.9 ±4.6%). The levels of IFN-gamma and CD69 expression on NK cells after GH treatment did not, however, approach that observed in control individuals: CD69 (IL-2 = 92 ±2%, IL-15 = 95.1 ±3.4%); IFN-gamma (IL-2 = 14.7 ± 8%, IL-15 = 18.2 ±5.4%)
Conclusions: Our results show that rHGH is capable of promoting increases in NK cell numbers, and can enhance their functional capacity in HIV-1+ individuals on HAART.