Interleukin-10 modulates proinflammatory cytokines in the human monocytic cell line THP-1 stimulated with Borrelia burgdorferi lipoproteins

We determined previously that lipoproteins of Borrelia burgdorferi stimulat e inflammatory and anti-inflammatory cytokines (interleukin-10 [IL-10]) in monocytes. IL-10 could have an effect on innate and acquired immune respons es 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 macrophage s is key, we investigated the effect of exogenous and endogenous IL 10 on t he production of the macrophage-derived cytokines IL-6, IL-1 beta, IL-12, a nd tumor necrosis factor alpha (TNF-alpha). We used the THP-1 human monocyt ic cell line and recombinant lipidated OspA (L-OspA) as the model target ce ll and stimulant, respectively. To determine the kinetics of cytokine produ ction by THP-1 cells, we stimulated them with L-OspA and also with heat-kil led B. burgdorferi cells (HBb) and lipopolysaccharide (LPS). Exogenous IL-1 0 dampened production of inflammatory cytokines, as elicited by lipoprotein s. The inhibition of endogenous IL-10 function by anti-IL-10 antibody reduc ed the production of IL-12 and IL-6 but not that of IL-1 beta and TNF-alpha . An inspection of the kinetics of cytokine production clarified this findi ng. TNF-alpha was produced prior to, and IL-beta was produced at the same t ime 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 reinforce s the notion that lipoproteins are the functional molecules in HBb and perh aps in vivo. It indicates also that signaling pathways utilized by LPS and lipoproteins may be extensively shared. The results are consistent with a m ajor role played by IL-10 in controlling the initial phase of infection wit h this spirochete.