Interleukin-10 Modulates Proinflammatory Cytokines in the Human Monocytic Cell Line THP-1 Stimulated withBorrelia burgdorferiLipoproteins
- 1 December 2000
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 68 (12), 6663-9
- https://doi.org/10.1128/iai.68.12.6663-6669.2000
Abstract
We determined previously that lipoproteins ofBorrelia burgdorferistimulate inflammatory and anti-inflammatory cytokines (interleukin-10 [IL-10]) in monocytes. IL-10 could have an effect on innate and acquired immune responses toB. burgdorferiand influence the magnitude of the infectious inoculum and disease outcome. To understand the mechanism(s) of IL-10 action during early infection, when innate immunity expressed chiefly by skin macrophages is key, we investigated the effect of exogenous and endogenous IL-10 on the production of the macrophage-derived cytokines IL-6, IL-1β, IL-12, and tumor necrosis factor alpha (TNF-α). We used the THP-1 human monocytic cell line and recombinant lipidated OspA (L-OspA) as the model target cell and stimulant, respectively. To determine the kinetics of cytokine production by THP-1 cells, we stimulated them with L-OspA and also with heat-killedB. burgdorfericells (HBb) and lipopolysaccharide (LPS). Exogenous IL-10 dampened production of inflammatory cytokines, as elicited by lipoproteins. The inhibition of endogenous IL-10 function by anti-IL-10 antibody reduced the production of IL-12 and IL-6 but not that of IL-1β and TNF-α. An inspection of the kinetics of cytokine production clarified this finding. TNF-α was produced prior to, and IL-β was produced at the same time as, IL-10, whereas IL-6 and IL-12 were produced later. HBb, LPS, and L-OspA yielded similar kinetics of cytokine production. This result reinforces the notion that lipoproteins are the functional molecules in HBb and perhaps in vivo. It indicates also that signaling pathways utilized by LPS and lipoproteins may be extensively shared. The results are consistent with a major role played by IL-10 in controlling the initial phase of infection with this spirochete.Keywords
This publication has 64 references indexed in Scilit:
- Mast cells and basophils in innate immunitySeminars in Immunology, 1998
- Studies on OspA: A source of new paradigms in Lyme disease researchTrends in Microbiology, 1998
- Mononeuropathy multiplex in rhesus monkeys with chronic lyme diseaseAnnals of Neurology, 1997
- Tumor Necrosis Factor: Function, Release and ClearanceCritical Reviews in Immunology, 1996
- Inhibition of the production and effects of interleukins‐1 and tumor necrosis factor α in rheumatoid arthritisArthritis & Rheumatism, 1995
- Animal models of Lyme disease: pathogenesis and immunoprophylaxisTrends in Microbiology, 1994
- Interleukin-10Annual Review of Immunology, 1993
- The Pathophysiology of Tumor Necrosis FactorsAnnual Review of Immunology, 1992
- Lyme DiseaseNew England Journal of Medicine, 1989
- ASSOCIATION BETWEEN TUMOUR NECROSIS FACTOR IN SERUM AND FATAL OUTCOME IN PATIENTS WITH MENINGOCOCCAL DISEASEThe Lancet, 1987