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Infection and Immunity, December 2000, p. 6663-6669, Vol. 68, No. 12
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Interleukin-10 Modulates Proinflammatory Cytokines
in the Human Monocytic Cell Line THP-1 Stimulated with
Borrelia burgdorferi Lipoproteins
P. K.
Murthy,
Vida A.
Dennis,*
Barbara L.
Lasater, and
Mario T.
Philipp
Department of Parasitology, Tulane Regional
Primate Research Center, Tulane University Health Sciences Center,
Covington, Louisiana
Received 19 June 2000/Returned for modification 7 August
2000/Accepted 28 August 2000
We determined previously that lipoproteins of Borrelia
burgdorferi stimulate inflammatory and anti-inflammatory
cytokines (interleukin-10 [IL-10]) in monocytes. IL-10 could have an
effect on innate and acquired immune responses to B. burgdorferi and 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-1
, IL-12, and tumor necrosis factor alpha (TNF-
). 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-killed B. burgdorferi cells (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-1
and TNF-
. An inspection of the kinetics of cytokine
production clarified this finding. TNF-
was produced prior to, and
IL-
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.
*
Corresponding author. Mailing address: Department of
Parasitology, Tulane Regional Primate Research Center, 18703 Three
Rivers Rd., Covington, LA 70433. Phone: (504) 871-6267. Fax: (504)
871-6390. E-mail: vida{at}tpc.tulane.edu.

Present address: Parasitology Division, Central Drug Research
Institute, Lucknow (U.P) 226001,
India.
Infection and Immunity, December 2000, p. 6663-6669, Vol. 68, No. 12
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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