In vivo effects of recombinant human interleukin-10 on lymphocyte phenotypes and leukocyte activation markers in inflammatory bowel disease.
BACKGROUND
Interleukin-10 (IL-10) exhibits potent anti-inflammatory and immunosuppressive activities in vitro. Recent data indicate that treatment with recombinant human IL-10 (rHuIL-10) Crohn's disease is safe and may induce clinical and endoscopic remission. The present study investigates the in vivo immunomodulatory properties of rHuIL-10 in inflammatory bowel disease (IBD).


METHODS
As part of two randomized, double-blinded, placebo-controlled trials, repeated flow cytometric analyses of lymphocyte phenotypes (CD3, CD4, CD8, CD16 + 56, CD19) and activity markers (human leukocyte antigen [HLA]-DR; intercellular adhesion molecule-1 [ICAM-1]; IL-2-receptor alpha [IL-2R alpha]; high affinity receptor for immunoglobulin G [IgG; Fc gamma RI]) on T cells, monocytes, and neutrophils were performed in 17 patients with IBD who received rHuIL-10 (5, 10, or 20 micrograms/kg) or placebo, administered subcutaneously, once daily for 28 days.


RESULTS
Minor changes were noted in CD3+, CD8+, and CD3+/CD16 + 56+ lymphocyte phenotypes, whereas absolute numbers of CD4+ lymphocytes and CD19+ cells increased. T-cell activation markers HLA-DR and IL-2R alpha were downregulated. rHuIL-10 did not influence HLA-DR expression on monocytes. ICAM-1 modulation on monocytes and neutrophils was mild and inconsistent. Fc gamma RI expression was upregulated on both neutrophils and monocytes.


CONCLUSIONS
These data indicate that the immunosuppressive effects of rHuIL-10 treatment are partly different from its in vitro observed actions. The increase of the cytotoxicity-mediating Fc gamma RI points to potential immunostimulating properties of this cytokine.
Dejaco
C
C
Department of Internal Medicine IV, University of Vienna, Austria. clemens.dejaco@akh-wien.ac.at
Reinisch
W
W
Lichtenberger
C
C
Waldhoer
T
T
Kuhn
I
I
Tilg
H
H
Gasche
C
C
D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D016753:Interleukin-10 / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D017452:Receptors, IgG / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology
D006684:HLA-DR Antigens; D007166:Immunosuppressive Agents; D017452:Receptors, IgG; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10