The objective of this research was to investigate whether immobilized anti-inflammatory cytokines will signal changes in the inflammatory profile of cultured monocytes. A fusion protein of recombinant human IL-1 receptor antagonist and elastin-like peptide (IL-1ra-ELP) was expressed in Escherichia coli. THP-1 human monocytes were cultured on either carboxyl-terminated self-assembled monolayers (SAMs), or SAMs with either covalently immobilized or soluble IL-1ra-ELP. LPS-stimulated monocytes exposed to either soluble or immobilized IL-1ra-ELP were prevented from cell differentiation, showed attenuated expression of pro-inflammatory cytokines, and had increased production of anti-inflammatory and pro-wound healing cytokines. These results suggest that immobilized anti-inflammatory cytokines have the potential to be immunomodulatory biomaterials.