Differential regulation of monocyte/macrophage cytokine production by pressure

Cytokine production by macrophages is essential for the inflammatory response. Normal human interstitial tissue pressure is 20 to 30 mm Hg, but generally decreases in acute inflammation.

We compared the effect of 20 mm Hg increased pressure (approximating normal interstitial tissue pressure) with that of ambient pressure (resembling pressure in inflamed tissues) on tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta production by undifferentiated (monocytic) and PMA (phorbol 12-, myristate 13-acetate)-differentiated (macrophage-like) THP-1 cells with or without lipopolysaccharide (LPS) (10 ng/mL).

Pressure stimulated spontaneous macrophage TNF-alpha secretion (30.5 +/- 6.3 vs. 49.1 +/- 2.8 pg/mL, P <.02), but not monocyte TNF-alpha secretion. Pressure did not stimulate IL-1beta release. As expected, LPS increased basal cytokine release. After LPS stimulation, pressure still tended to stimulate macrophage TNF-alpha, but inhibited monocyte TNF-alpha secretion (P <.05). In contrast, pressure inhibited IL-1beta release by both LPS-treated monocytes (986 +/- 134 vs. 595 +/- 226 pg/mL, P <.02) and macrophages (3,112 +/- 229 vs. 979 +/- 61 pg/mL, P <.01).

Extracellular pressure may regulate TNF-alpha and IL-1beta secretion differentially by monocytes and macrophages.