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Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
Surfactant protein A (SP-A) increases production of
proinflammatory cytokines by monocytic cells, including THP-1 cells, as
does lipopolysaccharide (LPS). Herein we report differences in
responses to these agents. First, polymyxin B inhibits the LPS response
but not the SP-A response. Second, SP-A-induced increases in tumor
necrosis factor-
(TNF-), interleukin-1
(IL-1), and IL-8 are
reduced by >60% if SP-A is preincubated with Survanta (200 µg/ml)
for 15 min before addition to THP-1 cells. However, the LPS
effects on TNF- and IL-8 are inhibited by <20% and the effect on
IL-1 by <50%. Third, at Survanta levels of 1 mg/ml, SP-A-induced
responses are reduced by >90%, and although the inhibitory effects on
LPS action increase, they still do not reach those seen with SP-A.
Finally, we tested whether SP-A could induce tolerance as LPS does.
Pretreatment of THP-1 cells with LPS inhibits their response to
subsequent LPS treatment 24 h later, including TNF-, IL-1,
and IL-8. Similar treatment with SP-A reduces TNF-, but IL-1 and
IL-8 are further increased by the second treatment with SP-A rather
than inhibited as with LPS. Thus, whereas both SP-A and LPS stimulate
cytokine production, their mechanisms differ with respect to inhibition
by surfactant lipids and in ability to induce tolerance.
surfactant protein A; lipopolysaccharide; cytokines; tolerance; innate immunity
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