Elevated levels of serum-soluble CD14 in human immunodeficiency virus type 1 (HIV-1) infection: correlation to disease progression and clinical events

Soluble (s) CD14, a marker for monocyte/macrophage activation and a m ediator of bacterial lipopolysaccharide (LPS) action, was elevated in serum from human immunodeficiency virus type 1 (HIV- 1)-infected ind ividuals (n = 92) compared with seronegative controls. The highest le vels were found in patients with advanced clinical and immunological disease. Patients with ongoing clinical events had significantly high er sCD14 levels than symptomatic HIV-1-infected individuals without c linical events, with especially elevated levels in patients infected with Mycobacterium avium complex (MAC). On longitudinal testing of pa tients (n = 26) with less than 100 x 10(6) CD4 lymphocytes/L at basel ine, we found that increasing sCD14 serum concentrations per time uni t were associated with death, whereas no differences in CD4 cell numb er decrease were found between survivors and nonsurvivors. In vitro s tudies showed that HIV-1 glycoprotein 120 and purified protein deriva tive (PPD) from M avium (MAC-PPD) stimulated normal monocytes to rele ase sCD14. Furthermore, MAC-PPD induced tumor necrosis factor (TNF) r elease from monocytes through interactions with CD14 and, importantly , the addition of sCD14 enhanced this MAC-PPD stimulatory effect. Our findings suggest that the CD14 molecule may be involved in the immun opathogenesis of HIV-1 infection, and it is conceivable that serial d etermination of sCD14 may give useful predictive information concerni ng disease progression and survival in HIV-1-infected patients. Copyr ight 1998 by The American Society of Hematology.