Serum Levels of Stem Cell Factor Are Increased in Asymptomatic Human Immunodeficiency Virus-Infected Patients and Are Associated With Prolonged Survival

Abstract

Cytopenia is a common complication of human immunodeficiency virus (HIV) infection and can affect different hematopoietic lineages, including erythropoiesis, lymphopoiesis, thrombopoiesis, and granulopoiesis. Stem cell factor (SCF), a cytokine expressed by bone marrow stromal cells, is a multipotential growth factor acting on early progenitor cells of most hematopoietic lineages. Therefore, we investigated the serum SCF levels in 74 HIV-infected persons without active secondary infection at different stages of HIV infection [Centers for Disease Control (CDC) stages A through C]. Circulating SCF levels were determined by enzyme-linked immunosorbent assay and were found to be significantly elevated in CDC stage A as compared with normal controls (7.18 +/- 1.94 ng/mL v 3.95 +/- 0.91 ng/mL, P = .04). However, in CDC groups B and C, SCF levels were lower than in CDC group A (3.29 +/- 0.75, P = .162, and 1.95 +/- 0.39, P = .005, respectively). Serum levels greater than 1.8 ng/mL were associated with a longer survival (P = .0037) in 74 HIV type 1 (HIV-1)-seropositive patients monitored for up to 114 weeks, suggesting that this cytokine may be directly associated with the disease course. A Cox proportional hazards model showed SCF to be an independent prognostic factor for survival (risk ratio for death, 0.73; 95% confidence interval, 0.56 to 0.95; P = .019). Serum SCF levels decreased on follow up in 24 of 38 patients or remained below 0.4 ng/mL in 10 of 38 patients from whom a second blood sample was collected after a mean interval of 44 weeks. To determine potential regulatory factors of SCF expression by stromal cells, we exposed cultured fibroblasts to various cytokines. Only interleukin-4 (IL-4) upregulated SCF mRNA. As IL-4 is modulated during early HIV disease, it may be a key regulator of SCF secretion. Further studies are required to elucidate the mechanism of SCF action and regulation in patients with HIV infection.