Impact of sepsis and HIV-1 infection on neutrophil radical production, lipids and lipoproteins

Sammanfattning: In clinical sepsis a decrease in total serum cholesterol caused by reduced HDL and LDL cholesterol occured early in the course of the infection with a normalisation after 2 months. This "sepsis HDL" was shown to contain the acute phase reactant SAA and it affected several functions of the neutrophil. However, the clearance of the exogenously delivered lipid emulsion, Intralipid, was found not to be impaired in infected patients with a hyperdynamic circulation. In HIV-1 infected patients, we observed an increased radical production by the neutrophils. High levels of malondialdehyde (MDA) in plasma, together with increased oxygen radical production by neutrophils and low plasma cysteine and glutathione levels, suggested the occurence of oxidative stress in such patients. Although treatment with the scavenger N acetylcysteine (NAC) reduced radical production in HIV-1-negative subjects, it did not change the radical production by neutrophils in HIV-1 infected patients. However, some other beneficial effects were found in the treatment study of HIV-1 patients. Thus plasma cysteine was normalised, the decrease in the number of CD4+ cells was counteracted and there was a decrease in TNFa. In contrast, NAC did not significantly reduce the high frequency of trimethopri-sulphamethoxazole (TMP-SMX)-induced drug reactions i n HIV-1-infected patients. However, low levels of plasma glutathione and plasma cysteine support the theory of antioxidant depletion when TMP SMX therapy creates a free sulpha metabolite radical and increases the oxidant burden.