IL-6, but not TNF-α, increases plasma YKL-40 in human subjects

Plasma levels of YKL-40 are elevated in patients with systemic infection, inflammatory disorders and cancer. Both monocytes/macrophages, neutrophils, and cancer cells have the capacity to produce YKL-40, but the regulation during the inflammatory response is unknown. To study the possible role of interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α in the regulation of YKL-40 plasma levels, we included healthy men, who received either recombinant human (rh)IL-6 (n = 6), rhTNF-α (n = 8) or vehicle (n = 7) for 3 h. The plasma levels of IL-6 and TNF-α reached ∼150 and ∼18 pg/ml, respectively, during the infusions. Following the IL-6 infusion, the plasma level of YKL-40 increased from ∼30 to ∼57 ng/ml (p < 0.05) at 24 h, and returned to normal values after 48 h. The plasma level of YKL-40 did not change during TNF-α infusion or infusion of vehicle. These data demonstrate that IL-6, but not TNF-α, has a key-role in the regulation of plasma YKL-40 levels during inflammation.