title: 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.
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine University Medical Center, Duesseldorf, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Manegold
authors.forename: H
authors.initials: H
authors.lastname: Jablonowski
authors.forename: C
authors.initials: C
authors.lastname: Armbrecht
authors.forename: G
authors.initials: G
authors.lastname: Strohmeyer
authors.forename: T
authors.initials: T
authors.lastname: Pietsch
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000097:blood; D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D015658:HIV Infections / Q000097:blood* / Q000150:complications / Q000401:mortality; D015497:HIV-1; D016298:Hematopoietic Cell Growth Factors / Q000097:blood*; D006525:Hepatitis, Viral, Human / Q000097:blood / Q000150:complications; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010198:Pancytopenia / Q000503:physiopathology*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D019089:Stem Cell Factor; D016019:Survival Analysis
chemical_list: D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors; D019089:Stem Cell Factor; D015847:Interleukin-4