Interleukin 8 modulates interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha release from normal human mononuclear cells.
Recombinant human interleukin 8 (IL-8) enhanced the release of inflammatory cytokines including interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) from normal human mononuclear cells in a dose-related manner (from 1 ng/ml to 10 ng/ml with a maximal effect at 5 ng/ml) when the cells incubated with IL-8 for 24 h. This cytokine-releasing activity of IL-8 is temperature-dependent and required protein synthesis since low temperature (4 degrees C) and cycloheximide (100 micrograms/ml) minimized the cytokine release from MNC. However, when IL-8 concentration was greater than 20 ng/ml, the cytokine release was suppressed. For further investigating the subcellular mechanism of the adverse effect of high dose IL-8 (20 ng/ml) in cytokine synthesis, human mononuclear cells (1 x 10(6)/ml) were stimulated with PHA (1 microgram/ml) in the presence of 20 ng/ml IL-8 for 3 days. We found not only [3H]thymidine incorporation of MNC was tremendously inhibited but DNA fragmentation appeared. Subsequently, the cell cycle of PHA-stimulated MNC retarded in the phase of G0/G1. These results suggest that in low concentration (5-10 ng/ml) IL-8 not only activated neutrophil phagocytosis but facilitated the release of inflammatory cytokines from mononuclear cells. Higher dose of IL-8 (more than 20 ng/ml) conversely suppressed these cytokine release from damaged cells by its cytotoxic effect. This newly found cytokine-releasing activity of IL-8 may play a role in the modulation of inflammation.
Yu
C L
CL
Department of Medicine, Veterans General Hospital-Taipei, National Yang-Ming Medical College, Taiwan, ROC.
Sun
K H
KH
Shei
S C
SC
Tsai
C Y
CY
Tsai
S T
ST
Wang
J C
JC
Liao
T S
TS
Lin
W M
WM
Chen
H L
HL
Yu
H S
HS
D002453:Cell Cycle / Q000187:drug effects; D002843:Chromatin / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013696:Temperature; D013936:Thymidine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D002843:Chromatin; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D010835:Phytohemagglutinins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003513:Cycloheximide; D013936:Thymidine