TNF-α and IL-1β but not IL-18 counteract TGF-β1 mediated stimulation of collagen accumulation and increased extracellular matrix strength and stiffness

Research Overview

Cytokine cross-talk between immune cells and fibroblasts drives the excess extracellular matrix that defines fibrosis. To separate the roles of three pro-inflammatory cytokines — TNF-α, IL-18, and IL-1β — this study used a 3D connective-tissue model: human fibroblasts seeded into circular agarose molds self-assembled into ring-shaped tissues and synthesized a collagen-rich matrix de novo, with each cytokine tested alone and together with TGF-β1 to mimic a fibrotic environment.

Tissues were analyzed at days 7 and 14 by histology, collagen and DNA content, and tensile testing for strength and stiffness. Despite their pro-inflammatory reputation, none of the cytokines increased collagen, alone or with TGF-β1. TNF-α and IL-1β actually reduced collagen, tissue strength, and stiffness — countering TGF-β1’s fibrotic stimulation — while IL-18 did not.