Exogenous recombinant human thioredoxin (rTRX, > or = 500 nM), a dithiol reductase enzyme, inhibited the expression of human immunodeficiency virus (HIV) 1BaL in human macrophages (M phi) by 71% (range, 26-100%), as evaluated by p24 antigen production and the integration of provirus at 14 d after infection. The stoichiometric reducing agent N-acetylcysteine (NAC) also inhibited HIV production, but to a lesser degree, and only at 30,000-fold higher concentrations. Exogenous rTRX is cleaved by M phi to generate the inflammatory cytokine, eosinophil cytotoxicity-enhancing factor (ECEF). In contrast to rTRX, rECEF (concentrations from 50 pM to 2 microM) enhanced the production of HIV by 67% (range, 33-92%). Thus, whereas TRX is a potent inhibitor of the expression of HIV in human M phi, cleavage of TRX to ECEF creates a mediator with the opposite effect. TRX also inhibited the expression of integrated provirus in the chronically infected OM 10.1 cell line, showing that it can act at a step subsequent to viral infection and integration.
Mycobacterium avium is one of the most prevalent opportunistic infections in AIDS patients, and neither prophylaxis nor treatment against M. avium is effective. To evaluate host defense mechanisms against mycobacterial infections, studies investigated whether neutrophils from AIDS patients could inhibit the growth of M. avium in vitro and what cytokines enhance neutrophil function against M. avium. Peripheral blood neutrophils from human immunodeficiency virus-negative and AIDS patients were incubated with media, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-8, or macrophage-inhibitory proteins and infected with M. avium, and the inhibition of bacterial growth was determined. G-CSF (1000 U/mL) and GM-CSF (2000 U/mL) stimulated neutrophils from AIDS patients to significantly inhibit M. avium growth. These results demonstrate that neutrophils from AIDS patients can respond to exogenously supplied G-CSF or GM-CSF by inhibiting the growth of M. avium.
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