Regulation by anti‐inflammatory cytokines (IL‐4, IL‐10, IL‐13, TGFβ)of interleukin‐8 production by LPS‐ and/ or TNFα‐activated human polymorphonuclear cells

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Abstract
The capacity to down‐regulate the production of IL‐8 by LPS‐activated human polymorphonuclear cells (PMN) has been demonstrated for IL‐4, IL‐10, and TGFβ. We compared their relative capacities and further extended this property to IL‐13. We report a great heterogeneity among individuals related to the responsiveness of PMN to the IL‐4 and IL‐13 inhibitory effects while their response to the IL‐10 effect was homogenous. The inhibitory activities were observed at the transcriptional level. IL‐8 induction by TNFα was, unlike its induction by LPS, resistant to the inhibitory effects of IL‐10, IL‐4, IL‐13 and TGFβ. Furthermore, IL‐10 and IL‐4 inhibitory activity were less effective when TNFα was acting synergistically with LPS to induce IL‐8 production by PMN. LPS‐induced cell‐associated IL‐8, detected in the PMN cultures, could be marginally inhibited by IL‐4 and IL‐10. Altogether, our data demonstrate that IL‐13 is able to inhibit LPS‐induced IL‐8 production by human PMN, although IL‐10 remains the most active anti‐inflammatory cytokine. Despite the capacity of IL‐4, IL‐10, and IL‐13 to limit the production of TNFα‐induced IL‐8 in a whole blood assay, none was able to inhibit this production when studying isolated human polymorphonuclear cells.