Effect of a four-week course of interleukin-10 on cytokine production in a placebo-controlled study of HIV-1-infected subjects.
Interleukin (IL)-10 suppresses synthesis of the pro-inflammatory cytokines tumor necrosis factor (TNF)alpha, IL-1beta, and interferon (IFN)gamma. Since pro-inflammatory cytokines have been implicated in the production of human immunodeficiency virus type 1 (HIV-1), cytokine synthesis in whole blood cultures were determined during a 4-week course of subcutaneous IL-10 injections in 33 HIV-1-infected patients. Patients were randomized into four groups: placebo (nine), IL-10 at 1 microg/kg/day (nine), IL-10 at 4 microg/kg/day (six) and IL-10 at 8 microg/kg three times per week (nine). Whole blood was obtained at the beginning and conclusion of the study and was stimulated for 24 hours with the combination of IL-18 plus lipopolysaccharide. TNFalpha production in stimulated whole blood was reduced three and six hours after the first injection of IL-10 compared to subjects injected with the placebo. After four weeks of treatment, production of IFNgamma was suppressed in a greater number of patients in the IL-10 treatment groups compared to subjects in the placebo group. Similarly, IL-1beta production was lower in the IL-10 treatment groups compared to subjects receiving placebo. In contrast, after four weeks of IL-10, circulating levels of the anti-inflammatory TNF soluble receptor p55 increased dose-dependently compared to placebo subjects. Patient heterogeneity and small sample size presented difficulties in establishing statistical significance. Although the cytokine changes in our study did not demonstrate statistically significant changes, the data nevertheless reveal that four weeks of IL-10 therapy in HIV-1 infected subjects produced the anticipated suppression of pro-inflammatory cytokines.
Pott
Gregory B
GB
Department of Medicine, Division of Infectious Diseases, University of Colorado at Denver and Health Sciences Center, 4200 E. 9th Ave. Box B168, Denver, CO 80262, USA.
Sailer
Carrie A
CA
Porat
Reuven
R
Peskind
Robert L
RL
Fuchs
Amy C
AC
Angel
Jonathan B
JB
Skolnik
Paul R
PR
Jacobson
Mark A
MA
Giordano
Michael F
MF
Lebeaut
Alexandre
A
Grint
Paul C
PC
Dinarello
Charles A
CA
Shapiro
Leland
L
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011446:Prospective Studies
D019380:Anti-HIV Agents; D016207:Cytokines; D053583:Interleukin-1beta; D010919:Placebos; D016753:Interleukin-10; D007371:Interferon-gamma