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)-⍺ and interleukin (IL)-1β 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-⍺ secretion (30.5 ± 6.3 vs. 49.1 ± 2.8 pg/mL, P <.02), but not monocyte TNF-⍺ secretion. Pressure did not stimulate IL-1β release. As expected, LPS increased basal cytokine release. After LPS stimulation, pressure still tended to stimulate macrophage TNF-⍺, but inhibited monocyte TNF-⍺ secretion (P <.05). In contrast, pressure inhibited IL-1β 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-⍺ and IL-1β secretion differentially by monocytes and macrophages.