SERUM CONCENTRATIONS OF SOLUBLE INTERCELLULAR-ADHESION MOLECULE-I AND PROGRESS TOWARDS DISEASE IN PATIENTS INFECTED WITH HIV

Intercellular adhesion molecule-1 (ICAM-1) is a membrane-bound molecule that is primarily involved in cell to cell adhesive interactions of the immune system. Concentrations of soluble ICAM-1 (s-ICAM-1) shed into the circulation were measured by a quantitative ELISA in HIV-infected persons without AIDS, patients with AIDS with or without evidence of acute opportunistic infection at the time of sampling, and HIV-seronegative patients with toxoplasmosis, community-acquired pneumonia, leishmaniasis and rickettsial infections. Patients were classified on the basis of clinical condition and CD4(+) T-cell counts according to the 1993 revised HIV classification of the USA Centers for Disease Control. Concentrations of s-ICAM-1 in the serum of HIV-infected persons without AIDS-indicator conditions (categories A1, A2, B1 and B2) as well as in the serum of patients with AIDS (categories A3, B3, C1, C2 and C3) were significantly higher than normal (mean +/- S.E.M. 469 +/- 23, n = 60 and 780 + 73, n = 56, respectively, versus 329 +/- ng/ml, P < 0.0001 and < 0.0001 respectively) and differed also significantly from each other (P < 0.0001). Raised concentrations of s-ICAM-1 in the serum of afebrile patients with AIDS but without acute opportunistic infection at the time of sampling (mean +/- S.E.M. 672 +/- 76, n = 29) did not differ from those of the remaining patients with AIDS or from those of HIV-seronegative patients with the infections studied. A steady and significant increase of serum concentrations of s-ICAM-1 with progress of disease according to clinical category (categories A double right arrow B double right arrow C, p = 0.0007) as well as with the loss of circulating CD4(+) T-cells (categories 1 double right arrow 2 double right arrow 3, P = 0.009) was observed. Individual serum concentrations of s-ICAM-1 showed negative correlations with individual total lymphocyte (P = 0004), CD4(+) T-cell (P = 0.05), CD8(+) T-cell counts (P = 0.03) as well as positive correlation with serum concentrations of soluble interleukin-2 receptors (P < 0.0001), an indirect marker of progress of HIV-related disease. Serum concentrations of s-ICAM-1 did not differ between patients with AIDS who were receiving or not receiving zidovudine at the time of sampling. A longitudinal survey is needed in order to determine whether measuring serum concentrations of s-ICAM-1, although not specific, has any predictive or prognostic value in these patients as well as whether this bioactive molecule has any pathogenetic role in the progress of disease in HIV infection.