ELEVATED LEVELS OF SERUM-SOLUBLE CD14 IN HUMAN-IMMUNODEFICIENCY-VIRUSTYPE-1 (HIV-1) INFECTION - CORRELATION TO DISEASE PROGRESSION AND CLINICAL EVENTS

Soluble (s) CD14. a marker for monocyte/macrophage activation and a me diator of bacterial lipopolysaccharide (LPS) action, was elevated in s erum from human immunodeficiency virus type 1 (HIV-1)-infected individ uals (n = 92) compared with seronegative controls. The highest levels were found in patients with advanced clinical and immunological diseas e. Patients with ongoing clinical events had significantly higher sCD1 4 levels than symptomatic HIV-1-infected individuals without clinical events, with especially elevated levels in patients infected with Myco bacterium avium complex (MAC). On longitudinal testing of patients (n = 26) with less than 100 x 10(6) CD4 lymphocytes/L at baseline, we fou nd that increasing sCD14 serum concentrations per time unit were assoc iated with death, whereas no differences in CD4 cell number decrease w ere found between survivors and nonsurvivors. In vitro studies showed that HIV-1 glycoprotein 120 and purified protein derivative (PPD) from M avium (MAC-PPD) stimulated normal monocytes to release sCD14. Furth ermore, MAC-PPD induced tumor necrosis factor (TNF) release from monoc ytes through interactions with CD14 and, importantly, the addition of sCD14,enhanced this MAC-PPD stimulatory effect. Our findings suggest t hat the CD14 molecule may be involved in the immunopathogenesis of HIV -1 infection, and it is conceivable that serial determination of sCD14 may give useful predictive information concerning disease progression and survival in HIV-1-infected patients. (C) 1998 by The American Soc iety of Hematology.